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

Academic Article

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 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 ceils. 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.
  • Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Borges M; Linnoila RI; Van De Velde HJK; Chen H; Nelkin BD; Mabry M; Baylin SB; Ball DW
  • Start Page

  • 852
  • End Page

  • 855
  • Volume

  • 386
  • Issue

  • 6627