Accession Number:

ADA439713

Title:

Egr1 Target Genes That Regulate Growth/Survival of Prostate Cells

Descriptive Note:

Annual summary rept. 1 Mar 2003-28 Feb 2005

Corporate Author:

BURNHAM INST LA JOLLA CA

Personal Author(s):

Report Date:

2005-03-01

Pagination or Media Count:

38.0

Abstract:

Last year I finished the study of the related co-activators p3OO and CBP. I have shown that the immediate early response TF, Egr1, acts upstream of p300CBP to induce or to repress transcription, depending on the stimulus. I have shown that serum stimulation of prostate cells results in cell growth by the up-regulation of p300CBP. In contrast, the stimulus of ultraviolet irradiation leads to cell cycle block and apoptosis through the inhibition of p300CBP. This year, I studied the effect of Egr1 on the expression of the related p73 and p53 tumor suppressor genes, having found several Egr1 binding sites in their promoters. Endogenous and exogenous Egr1 expression causes the transcriptional activation of the TAp73 isoforms from promoter Pi, and the modest activation of p53. The most notable finding was of positive feedback loops from both TAp73 and deltaNp73 isoforms and from p53 on Egr1 expression, strengthening our view that Egr1 is a tumor-suppressor by its genotoxic stress-responses that can substitute for the often mutant p53 in cancer cells. The interactive network between Egr1, p53, TAp73 and deltaNp73 explains how cancer cells make extensive responses to chemotherapy and irradiation even in the absence of wt p53.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Stress Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE