Accession Number:

ADB216187

Title:

Gene Activation by Antiestrogens Used in Breast Cancer Therapy Via the Interaction of Estrogen Receptor and AP-1.

Descriptive Note:

Annual rept. 1 Jul 95-30 Jun 96,

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

1996-07-01

Pagination or Media Count:

24.0

Abstract:

Tamoxifen-liganded estrogen receptor ER activates target genes regulated by AP-1 sites in uterine cells, an action that may underlie the estrogen-like side effects of tamoxifen. We tested the ER functions needed for this AP-l pathway. Point mutations in the ER AF-l or AF-2 interfere with ER action at a classical estrogen response element ERE, but do not hinder tamoxifen action at AP-l reporter genes. Similarly a point mutation that blocks ER dimerization is without effect on an AP-1 target. Deletion of the ER hinge region, which contains nuclear localization functions, blocks tamoxifen, but not estrogen action at AP-1. Although deletion of the DNA binding domain blocks tamoxifen action at AP-1, substitution of this domain with the DNA binding domain of the yeast GAL4 protein leaves tamoxifen activation of AP-1 targets. These results indicate that transcriptional activation, dimerization, and ERE binding functions of the ER are not needed for the tamoxifen-AP-1 pathway, and they reinforce the notion that this pathway operates by protein-protein interactions.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research
  • Organic Chemistry
  • Polymer Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE