Accession Number:

ADA339298

Title:

Translational Regulation of HER2 Gene Expression.

Descriptive Note:

Corporate Author:

FRED HUTCHINSON CANCER RESEARCH CENTERSEATTLE WA

Personal Author(s):

Report Date:

1997-12-01

Pagination or Media Count:

11.0

Abstract:

Amplification of the HER2 gene occurs in more than 20 of breast cancers and is associated with aggressive tumor cell growth. In addition to gene amplification, genetic mechanisms including translational deregulation may contribute to the overexpression of the HER2 oncoprotein. The HER2 mRNA contains a highly conserved short upstream open reading frame that represses downstream translation. Recent studies have shown that this upstream open reading frame represses translation of HER2 as well as a reporter gene cistron, and that it functions in mammalian cells, in yeast and in cell free translation extracts. Although the analysis of the mechanism by which the upstream open reading frame acts is not yet complete, the very short intercistronic spacing between the upstream open reading frame and the HER2 coding region is a critical component. Ribosomes that have translated the upstream open reading frame are unable to reinitiate efficiently at the HER2 initiation codon. The consequences of this translation mechanism for transforming activity of the HER2 protein synthesis are under investigation.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE