Download PDF
Horm Metab Res 2003; 35(11/12): 740-750
DOI: 10.1055/s-2004-814162
Review
© Georg Thieme Verlag Stuttgart · New York

The Insulin-like Growth Factor Axis in Cell Cycle Progression

J.  Dupont1 , A.  Pierre1 , P.  Froment1 , C.  Moreau1
  • 1Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Nouzilly, France
Further Information

Publication History

Received 26 August 2003

Accepted after Revision 25 September 2003

Publication Date:
07 January 2004 (online)

Also available at
    Permissions and Reprints

Abstract

Emerging evidence suggests that members of the Insulin-like Growth Factors (IGFs) family, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. Cancer cells exhibit an increased and deregulated proliferative activity. Abnormalities in many positive and negative modulators of the cell cycle are also frequent in many cancer types. Recent advances in the understanding of cell-cycle control mechanisms have been applied to outline the molecular mechanism through which IGFs regulate cell cycle progression. In this review, we will provide a brief overview of the role of the IGF system as a regulator of some components of the cell cycle.

Key words

Cancer - G1/S phase - IGF-IR - Signaling - Cell growth

References

  • 1 Sullivan K A, Castle V P, Hanash S M, Feldman E L. Insulin-like growth factor II in the pathogenesis of human neuroblastoma.  Am J Pathol. 1995;  147 1790-1798
    PubMedGoogle Scholar
  • 2 Toretsky J A, Helman L J. Involvement of IGF-II in human cancer.  J Endocrinol. 1996;  149 367-372
    CrossrefPubMedGoogle Scholar
  • 3 Sachdev D, Yee D. The IGF system and breast cancer.  Endocr Relat Cancer. 2001;  8 197-209
    CrossrefPubMedGoogle Scholar
  • 4 Moschos S J, Mantzoros C S. The role of the IGF system in cancer: from basic to clinical studies and clinical applications.  Oncology. 2002;  63 317-332
    CrossrefPubMedGoogle Scholar
  • 5 Ma J, Pollak M N, Giovannuci E, Chan J M, Tao Y, Hennekens C H, Stampfer M J. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3.  J Natl Cancer Ins. 1999;  91 620-625
    CrossrefPubMedGoogle Scholar
  • 6 Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer.  Nat Rev Cancer. 2001;  1 222-231
    CrossrefPubMedGoogle Scholar
  • 7 Sandhu C, Slingerland J. Deregulation of the cell cycle in cancer.  Cancer Detect Prev. 2000;  24 107-118
    PubMedGoogle Scholar
  • 8 Sherr C J. Cancer and cell cycles revisited.  Cancer Res. 2000;  60 3689-3695
    PubMedGoogle Scholar
  • 9 LeRoith D, Werner H, Beitner-Johnson D, Roberts C T Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor.  Endocr Rev. 1995;  16 143-163
    Google Scholar
  • 10 Clemmons D R. Insulin-like growth factor binding proteins and their role in controlling IGF actions.  Cytokine Growth Factor Rev. 1997;  8 45-62
    CrossrefPubMedGoogle Scholar
  • 11 Baker J, Liu J P, Robertson E J, Efstradiatis A. Role of insulin-like growth factors in embryonic and postnatal growth.  Cell. 1993;  75 73-82
    CrossrefPubMedGoogle Scholar
  • 12 Powell-Braxton L, Hollingshead P, Warburton C, Dowd M, Pitts-Meek S, Dalton D, Gillett N, Stewart T A. IGF-I is required for normal embryonic growth in mice.  Genes Dev. 1993;  7 2609-2617
    PubMedGoogle Scholar
  • 13 Yakar S, Liu J L, Stannard B, Butler A, Accili D, Sauer B, LeRoith D. Normal growth and development in the absence of hepatic insulin-like growth factor I.  Proc Natl Acad Sci U S A. 1999;  96 7324-7329
    CrossrefPubMedGoogle Scholar
  • 14 Sjogren K, Liu J L, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson O G, Jansson J O, Ohlsson C. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.  Proc Natl Acad Sci U S A. 1999;  96 7088-7092
    CrossrefPubMedGoogle Scholar
  • 15 DeChiara T, Efstratiadis A, Robertson E. A growth deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting.  Nature. 1990;  345 78-80
    CrossrefPubMedGoogle Scholar
  • 16 Baxter R C. Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex.  J Clin Endocrinol Metab. 1988;  67 65-272
    PubMedGoogle Scholar
  • 17 Boisclair Y R, Hurst K R, Ueki I, Tremblay M L, Ooi G T. Regulation and role of the acid-labile subunit of the 150-kilodalton insulin-like growth factor complex in the mouse.  Pediatr Nephrol. 2000;  14 562-566
    CrossrefPubMedGoogle Scholar
  • 18 Ferry R J Jr, Katz L E, Grimberg A, Cohen P, Weinzimer S A. Cellular actions of insulin-like growth factor binding proteins.  Horm Metab Res. 1999;  31 192-202
    PubMedGoogle Scholar
  • 19 Arai T, Busby W Jr, Clemmons D R. Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix.  Endocrinology. 1996;  137 4571-4575
    CrossrefPubMedGoogle Scholar
  • 20 Delbe J, Blat C, Desauty G, Harel L. Presence of IDF45 (mlGFBP-3) binding sites on chick embryo fibroblasts.  Biochem Biophys Res Commun. 1991;  179 495-501
    CrossrefPubMedGoogle Scholar
  • 21 Valentinis B, Bhala A, DeAngelis T, Baserga R, Cohen P. The human insulin-like growth factor (IGF) binding protein-3 inhibits the growth of fibroblasts with a targeted disruption of the IGF-I receptor gene.  Mol Endocrinol. 1995;  9 361-367
    CrossrefPubMedGoogle Scholar
  • 22 Baxter R C. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities.  Am J Physiol Endocrinol Metab. 2000;  278 E967-976
    PubMedGoogle Scholar
  • 23 Pavelic K, Bukovic D, Pavelic J. The role of insulin-like growth factor 2 and its receptors in human tumors.  Mol Med. 2002;  8 771-780
    PubMedGoogle Scholar
  • 24 McKinnon T, Chakraborty C, Gleeson L M, Chidiac P, Lala P K. Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK.  J Clin Endocrinol Metab. 2001;  86 3665-3675
    CrossrefPubMedGoogle Scholar
  • 25 Minniti C P, Kohn E C, Grubb J H, Sly W S, Oh Y, Muller H L, Rosenfeld R G, Helman L J. The insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor mediates IGF-II-induced motility in human rhabdomyosarcoma cells.  J Biol Chem. 1992;  267 9000-9004
    PubMedGoogle Scholar
  • 26 Ullrich A, Gray A, Tam A W, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.  Embo J. 1986;  10 2503-2512
    PubMedGoogle Scholar
  • 27 Hongo A, D’Ambrosio C, Miura M, Morrione A, Baserga R. Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor.  Oncogene. 1996;  12 1231-1238
    PubMedGoogle Scholar
  • 28 Li S, Resnicoff M, Baserga R. Effect of mutations at serines 1280 - 1283 on the mitogenic and transforming activities of the insulin-like growth factor I receptor.  J Biol Chem. 1996;  271 12 254-60.
    PubMedGoogle Scholar
  • 29 Miura M, Surmacz E, Burgaud J L, Baserga R. Different effects on mitogenesis and transformation of a mutation at tyrosine 1251 of the insulin-like growth factor I receptor.  J Biol Chem. 1995;  270 22 639-44
    PubMedGoogle Scholar
  • 30 Blakesley V A, Koval A P, Stannard B S, Scrimgeour A, LeRoith D. Replacement of tyrosine 1251 in the carboxyl terminus of the insulin-like growth factor-I receptor disrupts the actin cytoskeleton and inhibits proliferation and anchorage-independent growth.  J Biol Chem. 1998;  273 18 411-22
    PubMedGoogle Scholar
  • 31 Sun X J, Rothenberg P, Kahn C R, Backer J M, Araki E, Wilden P A, Cahill D A, Goldstein B J, White M F. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein.  Nature. 1991;  352 73-77
    CrossrefPubMedGoogle Scholar
  • 32 Patti M E, Sun X J, Bruening J C, Araki E, Lipes M A, White M F, Kahn C R. 4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice.  J Biol Chem. 1995;  270 24 670-24 673
    PubMedGoogle Scholar
  • 33 Lavan B E, Fantin V R, Chang E T, Lane W S, Keller S R, Lienhard G E. A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family.  J Biol Chem. 1997;  272 21 403-21 407
    PubMedGoogle Scholar
  • 34 Lavan B E, Lane W S, Lienhard G E. The 60-kDa phosphotyrosine protein in insulin-treated adipocytes is a new member of the insulin receptor substrate family.  J Biol Chem. 1997;  272 1439-11 443
    PubMedGoogle Scholar
  • 35 Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Grignani F, Pawson T, Pelicci P G. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction.  Cell. 1992;  70 93-104
    CrossrefPubMedGoogle Scholar
  • 36 Holgado-Madruga M, Emlet D R, Moscatello D K, Godwin A K, Wong A J. A Grb2-associated docking protein in EGF- and insulin-receptor signalling.  Nature. 1996;  379 560-564
    CrossrefPubMedGoogle Scholar
  • 37 Hermanto U, Zong C S, Li W, Wang L H. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix.  Mol Cell Biol. 2002;  22 2345-2365
    CrossrefPubMedGoogle Scholar
  • 38 Ligensa T, Krauss S, Demuth D, Schumacher R, Camonis J, Jaques G, Weidner K M. A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor.  J Biol Chem. 200;  276 33 419-33 427
    PubMedGoogle Scholar
  • 39 Moodie S A, Alleman-Sposeto J, Gustafson T A. Identification of the APS protein as a novel insulin receptor substrate.  J Biol Chem. 1999;  274 11 186-11 193
    PubMedGoogle Scholar
  • 40 Cai D, Dhe-Paganon S, Melendez P A, Lee J, Shoelson S E. Two New Substrates in Insulin Signaling, IRS5/DOK4 and IRS6/DOK5. J. Biol.  Chem. 2003;  278 25 323-25 330
    PubMedGoogle Scholar
  • 41 Lawlor M A, Alessi D R. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?.  J Cell Sci. 2001;  114 2903-2910
    PubMedGoogle Scholar
  • 42 Burgering B M, Medema R H. Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty.  J Leukoc Biol. 2003;  73 689-701
    CrossrefPubMedGoogle Scholar
  • 43 Maehama T, Taylor G S, Dixon J E. PTEN and myotubularin: novel phosphoinositide phosphatases.  Annu Rev Biochem. 2001;  70 247-79
    CrossrefPubMedGoogle Scholar
  • 44 Coolican S A, Samuel D S, Ewton D Z, McWade F J, Florini J R. The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways.  J Biol Chem. 1997;  272 6653-6662
    CrossrefPubMedGoogle Scholar
  • 45 Valverde A M, Teruel T, Lorenzo M, Benito M. Involvement of Raf-1 kinase and protein kinase C zeta in insulin-like growth factor I-induced brown adipocyte mitogenic signaling cascades: inhibition by cyclic adenosine 3’,5’-monophosphate.  Endocrinology. 1996;  137 3832-3841
    CrossrefPubMedGoogle Scholar
  • 46 Kuemmerle J F. IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase.  Am J Physiol Gastrointest Liver Physiol. 2003;  284 G411-G422
    PubMedGoogle Scholar
  • 47 Kuemmerle J F, Bushman T L. IGF-I stimulates intestinal muscle cell growth by activating distinct PI 3-kinase and MAP kinase pathways.  Am J Physiol. 1998;  275 G151-G158
    PubMedGoogle Scholar
  • 48 Dufourny B, Alblas J, van Teeffelen H A, van Schaik F M, van der Burg B, Steenbergh P H, Sussenbach J S. Mitogenic signaling of insulin-like growth factor I in MCF-7 human breast-cancer cells requires phosphatidylinositol 3-kinase and is independent of mitogen-activated protein kinase.  J Biol Chem. 1995;  23 589-23 597
    PubMedGoogle Scholar
  • 49 Misawa A, Hosoi H, Arimoto A, Shikata T, Akioka S, Matsumura T, Houghton P J, Sawada T. N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells.  Cancer Res. 2000;  60 64-69
    PubMedGoogle Scholar
  • 50 Misawa A, Hosoi H, Tsuchiya K, Sugimoto T. Rapamycin inhibits proliferation of human neuroblastoma cells without suppression of MycN.  Int J Cancer. 2003;  104 233-237
    CrossrefPubMedGoogle Scholar
  • 51 Thomas G. The S6 kinase signaling pathway in the control of development and growth.  Biol Res. 2002;  35 305-313
    PubMedGoogle Scholar
  • 52 Pearson R B, Thomas G. Regulation of p70s6k/p85s6k and its role in the cell cycle.  Prog Cell Cycle Res. 1995;  1 21-32
    PubMedGoogle Scholar
  • 53 Morgan D O. Cyclin-dependent kinases: engine, clocks, and microprocessors.  Annu Rev Cell Dev Biol. 1997;  13 261-291
    CrossrefPubMedGoogle Scholar
  • 54 Adams P D. Regulation of the retinoblastoma tumor suppressor protein by cyclin/CDKs.  Biochim Piophys Acta. 2001;  1471 123-133
    PubMedGoogle Scholar
  • 55 Hunter T, Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age.  Cell. 1994;  79 573-582
    CrossrefPubMedGoogle Scholar
  • 56 Grana X, Reddy P. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs).  Oncogene. 1995;  11 211-219
    PubMedGoogle Scholar
  • 57 Harbour J W, Dean D C. The pRb/E2F pathway: expanding roles and emerging paradigms.  Gene Dev. 2000;  14 2393-2409
    CrossrefPubMedGoogle Scholar
  • 58 Nigg E A. Cyclin-dependent kinase 7: at the cross-roads of transcription, DAN repair and cell cycle control?.  Curr Opin Cell Biol. 1996;  8 312-317
    CrossrefPubMedGoogle Scholar
  • 59 Ekholm S V, Reed S I. Regulation of G1, cyclin dependent kinase in the mammalian cell cycle.  Curr Opin Cell Biol. 2000;  12 676-684
    CrossrefPubMedGoogle Scholar
  • 60 Roussel M F. The INK4 family of cell cycle inhibitors in cancer.  Oncogene. 1999;  18 5311-5317
    CrossrefPubMedGoogle Scholar
  • 61 Nakayama K. Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development.  Bioessays. 1998;  20 1020-1029
    CrossrefPubMedGoogle Scholar
  • 62 Sherr C J, Roberts J M. CDK inhibitors: positive and negative regulators of G1-phase progression.  Genes Dev. 1999;  13 1501-1512
    CrossrefPubMedGoogle Scholar
  • 63 Slingerland J, Pagano M. Regulation of the cdk inhibitor p27 and its deregulation in cancer.  J Cell Physiol. 2000;  183 10-17
    CrossrefPubMedGoogle Scholar
  • 64 Rosenthal S, Cheng Z Q. Opposing early and late effects of insulin-like growth factor I on differentiation and the cell cycle regulatory retinoblastoma protein in skeletal myoblasts.  Proc Natl Acad sci USA. 1995;  92 10 307-10 311
    PubMedGoogle Scholar
  • 65 Dupont J, Karas M, LeRoith D. The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast-cancer cells includes cell cycle components.  J Biol Chem. 2000;  275 35 893-35 901
    PubMedGoogle Scholar
  • 66 Dufourny B, van Teeffelen H A, Hamelers I H, Sussenbach J S, Steenbergh P H. Stabilization of cyclin D1mRNA via the phosphatidylinositol 3-kinase pathway in MCF-7 human breast-cancer cells.  J Endocrinol. 2000;  166 329-338
    CrossrefPubMedGoogle Scholar
  • 67 Muise-Helmericks R C, Grimes H L, Bellacosa A, Malstrom S E, Tsichlis P N, Rosen N. Cyclin D expression is controlled post-transcriptionally via a phosphatidtlinositol 3-kinase/Akt-dependent pathway.  J Biol Chem. 1998;  273 29 864-29 872
    PubMedGoogle Scholar
  • 68 Diehl J A, Cheng A M, Roussel M F, Sherr C J. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.  Genes Dev. 1998;  12 3499-3511
    PubMedGoogle Scholar
  • 69 Hamelers I H, van Schaik R F, Sipkema J, Sussenbach J S, Steenbergh P H. Insulin-like growth factor I triggers nuclear accumulation of cyclin D1 in MCF-7S breast-cancer cells.  J Biol Chem. 2002;  277 47 645-47 652
    PubMedGoogle Scholar
  • 70 Zhu X, Kwon C H, Schlosshauer P W, Ellenson L H, Baker S J. PTEN induces G(1) cell cycle arrest and decreases cyclin D3 levels in endometrial carcinoma cells.  Cancer Res. 2001;  61 4569-4575
    PubMedGoogle Scholar
  • 71 Gottschalk A R, Basila D, Wong M, Dean N M, Brandts C H, Stokoe D, Haas-Kogan D A. p27Kip1 is required for PTEN-induced G1 growth arrest.  Cancer Res. 2001;  61 2105-2111
    PubMedGoogle Scholar
  • 72 Ramaswamy S N, Nakamura I, Sansal I, Bergeron L, Sellers W R. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR.  Cancer Cell. 2002;  2 81-91
    CrossrefPubMedGoogle Scholar
  • 73 Cheng M, Sexl V, Sherr C J, Roussel M F. Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1).  Proc Natl Acad Sci U S A. 1998;  95 1091-1096
    CrossrefPubMedGoogle Scholar
  • 74 Weber J D, Hu W, Jefcoat S C Jr, Raben D M, Baldassare J J. Ras-stimulated extracellular signal-related kinase 1 and RhoA activities coordinate platelet-derived growth factor-induced G1 progression through the independent regulation of cyclin D1 and p27.  J Biol Chem. 1997;  272 32 966-32 971
    PubMedGoogle Scholar
  • 75 Lavoie J N, L’Allemain G, Brunet A, Muller R, Pouyssegur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.  J Biol Chem. 1996;  271 20 608-20 616
    PubMedGoogle Scholar
  • 76 Weng L P, Smith W M, Brown J L, Eng C. PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model.  Hum Mol Genet. 2001;  10 605-616
    CrossrefPubMedGoogle Scholar
  • 77 Brisken C, Ayyannan A, Nguyen C, Heineman A, Reinhardt F, Tan J, Dey S K, Dotto G P, Weinberg R A, Jan T. IGF-II is a mediator of prolactin-induced morphogenesis in the breast.  Dev Cell. 2002;  3 877-887
    CrossrefPubMedGoogle Scholar
  • 78 Zhang W, Lee J C, Kumar S, Gowen M. ERK pathway mediates the activation of Cdk2 in IGF-I-induced proliferation of human osteosarcoma MG-63 cells.  J Bone Miner Res. 1999;  14 528-535
    PubMedGoogle Scholar
  • 79 Machida S, Spangenburg E E, Booth F W. Forkhead transcription factor FoxO1 transduces insulin-like growth factor’s signal to p27KIP1 in primary skeletal muscle satellite cells.  Journal of Cellular Physiology. 2003;  196 523-531
    CrossrefPubMedGoogle Scholar
  • 80 Spangenburg E E, Chakravarthy M V, Booth F W. p27Kip1: a key regulator of skeletal muscle satellite cell proliferation.  Clin Orthop. 2002;  403 S221-227
    PubMedGoogle Scholar
  • 81 Ewton D Z, Kansra S, Lim S, Friedman E. Insulin-like growth factor-I has a biphasic effect on colon carcinoma cells through transient inactivation of forkhead1, initially mitogenic, then mediating growth arrest and differentiation.  Int J Cancer. 2002;  98 665-673
    CrossrefPubMedGoogle Scholar
  • 82 Medema R H, Kops G J, Bos J L, Burgenring B M. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.  Nature. 2000;  404 782-787
    CrossrefPubMedGoogle Scholar
  • 83 Dijkers P F, Medema R H, Pals C, Banerji L, Thomas N S, Lam E W, Burgering B M, Raaijmakers J A, Lammers J W, Koenderman L, Coffer P J. Forkhead transcription f actor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1).  Mol Cell Biol. 2000;  20 9138-9148
    CrossrefPubMedGoogle Scholar
  • 84 Mamillapalli R, Gavrilova N, Mihaylova V T, Tsvetkov L M, Wu H, Zhang H, Sun H. PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2).  Curr Biol. 2001;  11 263-267
    CrossrefPubMedGoogle Scholar
  • 85 Pagano M, Tam S W, Theodoras A M, Beer-Romero P, Del Sal G, Chau V, Yew P R, Draetta G F, Rolfe M. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27.  Science. 1995;  269 682-685
    PubMedGoogle Scholar
  • 86 Fujita N, Sato S, Katayama K, Tsuruo T. Akt-dependent phosphorylation of p27Kip1 promotes binding to 14 - 3-3 and cytoplasmic localization.  J Biol Chem. 2002;  277 28 706-28 713
    PubMedGoogle Scholar
  • 87 Carrano A C, Eytan E, Hershko A, Pagano M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.  Nat Cell Biol. 1999;  1 193-199
    CrossrefPubMedGoogle Scholar
  • 88 Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama K I. Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export.  J Biol Chem. 2002;  277 14 355-143 558
    PubMedGoogle Scholar
  • 89 Kanter-Lewensohn L, Dricu A, Girnita L, Wejde J, Larsson O. Expression of insulin-like growth factor-1 receptor (IGF-IR) and p27Kip1 in melanocytic tumors: a potential regulatory role of IGF-I pathway in distribution of p27Kip1 between different cyclins.  Growth Factors. 2000;  17 193-202
    CrossrefPubMedGoogle Scholar
  • 90 von Harsdorf R, Hauck L, Mehrhof F, Wegenka U, Cardoso M C, Dietz R. E2F-1 overexpression in cardiomyocytes induces downregulation of p21CIP1 and p27KIP1 and release of active cyclin-dependent kinases in the presence of insulin-like growth factor I.  Circ Res. 1999;  85 128-136
    PubMedGoogle Scholar
  • 91 Kodama Y, Baxter R C, Martin J L. Insulin-like growth factor-I inhibits cell growth in the a549 non-small lung cancer cell line.  Am J Respir Cell Mol Biol. 2002;  27 336-344
    PubMedGoogle Scholar
  • 92 Dupont J, Karas M, LeRoith D. The cyclin dependent kinase inhibitor p21CIP/WAF is a positive regulator of IGF-I-induced cell proliferation in MCF-7 human breast-cancer cells.  J Biol Chem. 2003;  278 37 256-37 264
    PubMedGoogle Scholar
  • 93 Lai A, Sarcevic B, Prall O W, Sutherland R L. Insulin/insulin-like growth factor-I and estrogen cooperate to stimulate cyclin E-Cdk2 activation and cell Cycle progression in MCF-7 breast-cancer cells through differential regulation of cyclin E and p21(WAF1/Cip1).  J Biol Chem. 2001;  276 25 823-25 833
    PubMedGoogle Scholar
  • 94 Cheng M, Olivier P, Diehl J A, Fero M, Roussel M F, Roberts J M, Sherr C J. The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts.  Embo J. 1999;  18 1571-1583
    CrossrefPubMedGoogle Scholar
  • 95 LaBaer J, Garrett M D, Stevenson L F, Slingerland J M, Sandhu C, Chou H S, Fattaey A, Harlow E. New functional activities for the p21 family of CDK inhibitors.  Genes Dev. 1997;  11 847-862
    PubMedGoogle Scholar
  • 96 Weiss R H, Joo A, Randour C. p21(Waf1/Cip1) is an assembly factor required for platelet-derived growth factor-induced vascular smooth muscle cell proliferation.  J Biol Chem. 2000;  275 10 285-10 290
    PubMedGoogle Scholar
  • 97 Bourcigaux N, Gaston V, Logie A, Bertagna X, Le Bouc Y, Gicquel C. High expression of cyclin E and G1 CDK and loss of function of p57KIP2 are involved in proliferation of malignant sporadic adrenocortical tumors.  J Clin Endocrinol Metab. 2000;  85 322-330
    CrossrefPubMedGoogle Scholar
  • 98 Grandjean V, Smith J, Schofield P N, Ferguson-Smith A C. Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome.  Proc Natl Acad Sci USA. 2000;  97 5279-5284
    CrossrefPubMedGoogle Scholar
  • 99 Pardee A B. Gi events and regulation of cell proliferation.  Science. 1989;  246 603-608
    PubMedGoogle Scholar
  • 100 Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T. Effect of a null mutation of the type I IGF receptor gene on growth and transformation of mouse embryo fibroblasts.  Mol Cell Biol. 1994;  14 3604-3612
    PubMedGoogle Scholar
  • 101 Adesanya O O, Zhou J, Samathanam C, Powell-Braxton L, Bondy C A. Insulin-like growth factor 1 is required for G2 progression in the estradiol-induced mitotic cycle.  Proc Natl Acad Sci USA. 1999;  96 3287-3291
    CrossrefPubMedGoogle Scholar
  • 102 Morrione A, Valentinis B, Resnicoff M, Xu S, Baserga R. The role of mGrb10alpha in insulin-like growth factor I-mediated growth.  J Biol Chem. 1997;  272 26 382-26 387
    PubMedGoogle Scholar
  • 103 Labbe J C, Picard A, Peaucellier G, Cavadore J C, Nurse P, Doree M. Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation.  Cell. 1989;  57 253-263
    CrossrefPubMedGoogle Scholar
  • 104 Furlanetto R W, Harwell S E, Frick K K. Insulin-like growth factor-I induces cyclin-D1 expression in MG63 human osteosarcoma cells in vitro. .  Mol Endocrinol. 1994;  8 510-517
    CrossrefPubMedGoogle Scholar
  • 105 Surmacz E, Nugent P, Pietrzkowski Z, Baserga R. The role of the IGF1 receptor in the regulation of cdc2mRNA levels in fibroblasts.  Exp Cell Res. 1992;  199 275-278
    CrossrefPubMedGoogle Scholar
  • 106 Ellis M J, Leav B A, Yang Z, Rasmussen A, Pearce A, Zweibel J A, Lippman M E, Cullen K J. Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast-cancer cells.  Mol Endocrinol. 1996;  10 286-297
    CrossrefPubMedGoogle Scholar
  • 107 van der Burg B, Rutteman G R, Blankenstein M A, de Laat S W, van Zoelen E J. Mitogenic stimulation of human breast-cancer cells in a growth factor-defined medium: synergistic action of insulin and estrogen.  J Cell Physiol. 1988;  134 101-108
    CrossrefPubMedGoogle Scholar
  • 108 Stewart A J, Johnson M D, May F E, Westley B R. Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast-cancer cells.  J Biol Chem. 1990;  265 21 172-21 178
    PubMedGoogle Scholar
  • 109 Lee A V, Jackson J G, Gooch J L, Hilsenbeck S G, Coronado-Heinsohn E, Osborne C K, Yee D. Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo.  Mol Endocrinol. 1999;  13 787-796
    CrossrefPubMedGoogle Scholar
  • 110 Hamelers I H, Steenbergh P H. Interactions between estrogen and insulin-like growth factor signaling pathways in human breast tumor cells.  Endocr Relat Cancer. 2003;  10 331-345
    CrossrefPubMedGoogle Scholar
  • 111 Benassi M S, Molendini L, Gamberi G, Magagnoli G, Ragazzini P, Gobbi G A, Sangiorgi L, Pazzaglia L, Asp J, Brantsing C, Picci P. Involvement of INK4A gene products in the pathogenesis and development of human osteosarcoma.  Cancer. 2001;  92 3062-3067
    CrossrefPubMedGoogle Scholar
  • 112 Kanoe H, Nakayama T, Murakami H, Hosaka T, Yamamoto H, Nakashima Y, Tsuboyama T, Nakamura T, Sasaki M S, Toguchida J. Amplification of the CDK4 gene in sarcomas: tumor specificity and relationship with the RB gene mutation.  Anticancer Res. 1998;  18 2317-2321
    PubMedGoogle Scholar
  • 113 Spirin K S, Simpson J F, Takeuchi S, Kawamata N, Miller C W, Koeffler H P. p27/Kip1 mutation found in breast cancer.  Cancer Res. 1996;  56 2400-2404
    PubMedGoogle Scholar
  • 114 Lung J C, Chu J S, Yu J C, Yue C T, Lo Y L, Shen C Y, Wu C W. Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability.  Genes Chromosomes Cancer. 2002;  34 276-284
    CrossrefPubMedGoogle Scholar
  • 115 An H X, Beckmann M W, Reifenberger G, Bender H G, Niederacher D. Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation.  Am J Pathol.. 1999;  154 113-118
    PubMedGoogle Scholar
  • 116 Borg A, Zhang Q X, Alm P, Olsson H, Sellberg G. The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression.  Cancer Res. 1992;  52 2991-2994
    PubMedGoogle Scholar
  • 117 Guo S S, Wu X, Shimoide A T, Wong J, Sawicki M P. Anomalous overexpression of p27(Kip1) in sporadic pancreatic endocrine tumors.  J Surg Res. 2001;  96 284-288
    CrossrefPubMedGoogle Scholar
  • 118 Ebert M P, Hernberg S, Fei G, Sokolowski A, Schulz H U, Lippert H, Malfertheiner P. Induction and expression of cyclin D3 in human pancreatic cancer.  J Cancer Res Clin Oncol. 2001;  127 449-454
    CrossrefPubMedGoogle Scholar
  • 119 Gerdes B, Ramaswamy A, Ziegler A, Lang S A, Kersting M, Baumann R, Wild A, Moll R, Rothmund M, Bartsch D K. p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb.  Ann Surg. 2002;  235 51-59
    CrossrefPubMedGoogle Scholar
  • 120 Nitti D, Belluco C, Mammano E, Marchet A, Ambrosi A, Mencarelli R, Segato P, Lise M. Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome.  J Surg Oncol. 2002;  81 167-175
    CrossrefPubMedGoogle Scholar
  • 121 Schneider-Stock R, Boltze C, Lasota J, Miettinen M, Peters B, Pross M, Roessner A, Gunther T. High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors.  J Clin Oncol. 2003;  21 1688-1697
    CrossrefPubMedGoogle Scholar
  • 122 Liang B, Wang S, Yang X, Ye Y, Yu Y, Cui Z. Expressions of cyclin E, cyclin dependent kinase 2 and p57(KIP2) in human gastric cancer.  Chin Med J (Engl). 2003;  116 20-23
    PubMedGoogle Scholar
  • 123 Tahara E. Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis.  Cancer. 1995;  75 1410-1417
    PubMedGoogle Scholar
  • 124 Chetty R. p27 Protein and cancers of the gastrointestinal tract and liver: an overview.  J Clin Gastroenterol. 2003;  37 23-27
    CrossrefPubMedGoogle Scholar
  • 125 Jin M, Piao Z, Kim N G, Park C, Shin E C, Park J H, Jung H J, Kim C G, Kim H. p16 is a major inactivation target in hepatocellular carcinoma.  Cancer. 2000;  89 60-68
    CrossrefPubMedGoogle Scholar
  • 126 Qin L X, Tang Z Y. The prognostic molecular markers in hepatocellular carcinoma.  World J Gastroenterol. 2002;  8 385-392
    PubMedGoogle Scholar
  • 127 Fernandez P L, Hernandez L, Farre X, Campo E, Cardesa A. Alterations of cell cycle-regulatory genes in prostate cancer.  Pathobiology. 2002;  70 1-10
    CrossrefPubMedGoogle Scholar
  • 128 Payton M, Scully S, Chung G, Coats S. Deregulation of cyclin E2 expression and associated kinase activity in primary breast tumors.  Oncogene. 2002;  21 8529-8534
    CrossrefPubMedGoogle Scholar
  • 129 Bartkova J, Rajpert-de Meyts E, Skakkebaek N E, Bartek J. D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy.  J Pathol. 1999;  187 573-581
    PubMedGoogle Scholar
  • 130 Fujita M, Enomoto T, Haba T, Nakashima R, Sasaki M, Yoshino K, Wada H, Buzard G S, Matsuzaki N, Wakasa K, Murata Y. Alteration of p16 and p15 genes in common epithelial ovarian tumors.  Int J Cancer. 1997;  74 148-155
    CrossrefPubMedGoogle Scholar
  • 131 Sasano H, Comerford J, Silverberg S G, Garrett C T. An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma.  Cancer. 1990;  66 2150-2154
    PubMedGoogle Scholar
  • 132 Chakravarthy M V, Abraha T W, Schwartz R J, Fiorotto M L, Booth F W. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3’-kinase/Akt signaling pathway.  J Biol Chem. 2000;  275 35 942 - 35 952
    PubMedGoogle Scholar
  • 133 Takahashi Y, Tobe K, Kadowaki H, Katsumata D, Fukushima Y, Yazaki Y, Akanuma Y, Kadowaki T. Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts.  Endocrinology. 1997;  138 741-750
    CrossrefPubMedGoogle Scholar
  • 134 Kurihara S, Hakuno F, Takahashi S. Insulin-like growth factor-I-dependent signal transduction pathways leading to the induction of cell growth and differentiation of human neuroblastoma cell line SH-SY5Y: the roles of MAP kinase pathway and PI 3-kinase pathway.  Endocr J. 2000;  47 739-751
    CrossrefPubMedGoogle Scholar
  • 135 Talavera F, Bergman C, Pearl M L, Connor P, Roberts J A, Menon K M. cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle.  Cell Prolif. 1995;  28 121-136
    PubMedGoogle Scholar
  • 136 Yoshinouchi M, Baserga R. The role of the IGF-I receptor in the stimulation of cells by short pulses of growth factors.  Cell Prolif. 1993;  26 139-146
    PubMedGoogle Scholar
  • 137 Krystal G W, Sulanke G, Litz J. Inhibition of phosphatidylinositol 3-kinase-Akt signaling blocks growth, promotes apoptosis, and enhances sensitivity of small cell lung cancer cells to chemotherapy.  Mol Cancer Ther. 2002;  1 913-922
    PubMedGoogle Scholar
  • 138 Satyamoorthy K, Li G, Vaidya B, Patel D, Herlyn M. Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and beta-catenin pathways.  Cancer Res. 2001;  61 7318-7324
    PubMedGoogle Scholar
  • 139 El-Badry O M, Helman L J, Chatten J, Steinberg S M, Evans A E, Israel M A. Insulin-like growth factor II-mediated proliferation of human neuroblastoma.  J Clin Invest. 1991;  87 648-657
    PubMedGoogle Scholar

J. Dupont, Ph. D.

Unité de Physiologie de la Reproduction et des Comportements

Institut National de la Recherche Agronomique · Nouzilly 37 380 · France

Phone: + 33 (2) 47 42 79 64

Fax: + 33 (2) 47 42 77 43

Email: jdupont@tours.inra.fr

      >