Accession Number:

ADB281613

Title:

Novel Transcriptional Interactions Between the Estrogen and Retinoic Acid Receptors in Human Breast Cancer Cells

Descriptive Note:

Annual summary rept. 1 Jun 1998-31 May 2001

Corporate Author:

MCGILL UNIV MONTREAL (QUEBEC)

Personal Author(s):

Report Date:

2001-06-01

Pagination or Media Count:

18.0

Abstract:

The purpose of this research was to investigate the specific mechanisms by which transcriptional pathways may become more responsive to retinoids in cells that express the estrogen receptor SR. To determine which region of ER is required for retinoid sensitivity, several deletion mutants of ER were subcloned into a retroviral vector and stable ER-deletion mutant human breast cancer cell lines were derived. Studies with these stable cell lines indicate that the N-terminal region of ER is required to potentiate the retinoid response. Like wild-type ER positive cells, C-terminal deletion mutants are growth inhibited by retinoids and give a greater than 100 fold induction on a RARE compared to the retroviral control. These results indicate that the restored response to RA is mediated by the N-terminal of ER. Blocking the AF1 domain with 101 diminishes the effect of ER on transcription from a RARE. Activation of AF1 may play an important role in the cross-talk between ER and RAR pathways. We are currently investigating the phosphorylation state of ER in the N-terminal and using kinase inhibitors in combination with RA to determine if these two agents could synergize to inhibit breast cancer cell growth.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE