| First Author | Borges M | Year | 1997 |
| Journal | Nature | Volume | 386 |
| Issue | 6627 | Pages | 852-5 |
| PubMed ID | 9126746 | Mgi Jnum | J:113000 |
| Mgi Id | MGI:3664178 | Doi | 10.1038/386852a0 |
| Citation | Borges M, et al. (1997) An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 386(6627):852-5 |
| abstractText | 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 differentiation. 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 population. 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. |
