Human achaete-scute homologue 1 (HASH-1) is downregulated in differentiating neuroblastoma cells

Biochem Biophys Res Commun. 1999 Mar 24;256(3):557-63. doi: 10.1006/bbrc.1999.0314.

Abstract

The mammalian achaete-scute homologue, MASH-1, is crucial for early development of the sympathetic nervous system and is transiently expressed in sympathetic neuroblasts during embryogenesis. Here we report that the human homologue (HASH-1) was expressed in all analyzed cell lines (6/6) derived from the sympathetic nervous system tumor neuroblastoma. The majority of small-cell lung carcinoma (4/5) cell lines tested expressed HASH-1, while other nonneuronal/non-neuroendocrine cell lines were negative. Induced differentiation of neuroblastoma cells resulted in HASH-1 downregulation. This occurred concomitant with induction of neurite outgrowth and expression of the neuronal marker genes GAP-43 and neuropeptide Y. Constitutive expression of exogenous HASH-1 did not alter the capacity of the neuroblastoma cells to differentiate in response to differentiation-inducing agents. It is concluded that moderate HASH-1 expression does not compromise the capacity of these cells to differentiate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Northern
  • Carcinoma, Small Cell
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cell Differentiation / drug effects
  • Cell Size / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation* / drug effects
  • GAP-43 Protein / analysis
  • GAP-43 Protein / metabolism
  • Growth Substances / pharmacology
  • Humans
  • Lung Neoplasms
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Neurites / drug effects
  • Neurites / metabolism
  • Neuroblastoma
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuropeptide Y / analysis
  • Neuropeptide Y / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptor, trkA*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • DNA-Binding Proteins
  • GAP-43 Protein
  • Growth Substances
  • Membrane Proteins
  • Neuropeptide Y
  • RNA, Messenger
  • Transcription Factors
  • Tretinoin
  • Receptor, trkA
  • Tetradecanoylphorbol Acetate