Accession Number:

ADA433937

Title:

Control of Breast Carcinoma Angiogenesis by Nutrient Stress Mechanisms

Descriptive Note:

Final rept. 1 Aug 2003-31 Jul 2004

Corporate Author:

NEW MEXICO UNIV ALBUQUERQUE

Personal Author(s):

Report Date:

2004-08-01

Pagination or Media Count:

41.0

Abstract:

We found that expression of the pro-angiogenic gene vascular endothelial growth factor VEGF by breast cancer cell lines is responsive to endoplasmic reticulum ER stress and deprivation of nutrients, including glucose and amino acids. This means that VEGF expression in solid tumors may be increased not just by hypoxia, but also by deficient delivery of other nutrients. We have published three manuscripts on this subject. However, we have been unable to determine the precise mechanism by which VEGF expression is lines. We have tested the role of several signal transduction pathways and transcription factors that are part of the unfolded protein response UPR. This response signals the expression of genes that are upregulated in response to may ER stresses and glucose deprivation. We found that the transcription factor ATF4 plays an important role in VEGF expression of some cells in response to ER stress. However, ATF4 is not necessary for the response to amino acid glutamine deprivation and glucose deprivation of breast cancer cell lines. Thus, the mechanism by which deprivation of glucose and amino acids upregulate VEGF expression by breast cancer cells is still unknown.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE