Accession Number : ADA300397

Title :   Estrogen Receptor Accessory Factors in Breast Cancer Cells.

Descriptive Note : Annual rept. 25 Jul 94-24 Jul 95,

Corporate Author : CHICAGO UNIV IL

Personal Author(s) : Greene, Geoffrey L.

PDF Url : ADA300397

Report Date : 22 AUG 1995

Pagination or Media Count : 63

Abstract : HE GOAL OF THIS INVESTIGATION IS TO DETERMINE THE ROLE OF ACCESSORY PROTEINS AS MEDIATORS OF ESTROGEN RECEPTOR (ER) activity both before and after ER interaction with specific DNA binding sites (EREs) on responsive genes. We wish to test the hypothesis that estrogens and estrogen antagonists promote altered ER-accessory protein interactions that lead to differential transcriptional activity. During the past year, we have characterized (by gel retardation analysis, filter binding as says, and DNA bending experiments) ER- associated proteins isolated by specific DNA (ERE) affinity chromatography, steroid affinity chromatography, and immunoadsorption from CHO-ER and MCF-7 breast cancer cell extracts. A major effect of of four such proteins (p45, p48, p55, and hsp7O) in in vitro ER-ERE reconstitution experiments is to facilitate maximal ER-ERE interaction (capacity). Second, these proteins appear to contribute to the bend angle induced by ER interaction with EREs, which in turn may affect the rate of transcription initiation of responsive genes. We have also used a OST-ER ligand binding domain (LBD) fusion protein to identify additional proteins in mammalian cell extracts that bind to or modulate ER selectively in the presence of estrogen agonists or antagonists. At least one of these proteins phosphorylates ER-LBD in an in vitro kinase assay. Work is in progress to identify this kinase, as well as p45 and p48, and to determine their roles in agonist/antagonist- mediated ER function in hormone responsive breast cancer cells.

Descriptors :   *CELLS(BIOLOGY), *PHARMACOLOGICAL ANTAGONISTS, *MAMMARY GLANDS, *ESTROGENS, *BREAST CANCER, MAMMALS, PROTEINS, DEOXYRIBONUCLEIC ACIDS, GENES, FILTERS, HYPOTHESES, GELS, SENSE ORGANS, CHROMATOGRAPHY, RETARDATION, STEROIDS.

Subject Categories : Biology
      Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE