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An achaete-scute homologue essential for neuroendocrine differentiation in the lung

Abstract

In Drosophila and in vertebrates, the achaete-scute family of basic helix–loop–helix transcription factors plays a critical developmental role in neuronal commitment and differentiation1–6. Relatively little is known, however, about the transcriptional control of neural features in cells outside a neuronal context. A minority of normal bronchial epithelial cells and many lung cancers, especially small-cell lung cancer, exhibit a neuroendocrine phenotype that may reflect a common precursor cell population7–11. We show here that human achaete-scute homologue-–1 (hASH1) is selectively expressed in normal fetal pulmonary neuroendocrine cells, as well as in the diverse range of lung cancers with neuroendocrine features. Strikingly, newborn mice bearing a disruption of the ASH1 gene have no detectable pulmonary neuroendocrine cells. Depletion of this transcription factor from lung cancer cells by antisense oligonucleotides results in a significant decrease in the expression of neuroendrocrine markers. Thus, a homologue of Drosophila neural fate determination genes seems to be necessary for progression of lung epithelial cells through a neuroendocrine differentiation pathway that is a feature of small-cell lung cancer, the most lethal form of human lung cancer.

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Borges, M., Linnoila, R., van de Velde, H. et al. An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 386, 852–855 (1997). https://doi.org/10.1038/386852a0

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