Accession Number : ADA311359

Title :   Factors that Effect Signal Transduction by the Estrogen Receptor.

Descriptive Note : Annual rept. 1 Oct 94-30 Sep 95,

Corporate Author : NEW YORK UNIV MEDICAL CENTER NY

Personal Author(s) : Garabadian, Michael J.

PDF Url : ADA311359

Report Date : OCT 1995

Pagination or Media Count : 23

Abstract : This project examines the mechanism of signal transduction by the estrogen receptor (ER), a hormone dependent transcriptional regulator involved in many human breast tumors. We have found that ectopic expression of the cyclin A/cdk2 kinase complex increases hormone-dependent transcriptional activity by the estrogen receptor in vivo. This effect can be further enhanced by the concurrent expression of cyclin-dependent kinase activators, CAKs, and abolished by coexpression of the cdk inhibitor (CDI), p27. Likewise, ER-dependent transcriptional activation is reduced by the expression of a dominant negative cdk2 mutant in mammalian cells or by deletion of a potential cyclin A homologue, Clb4, in yeast. ER is also phosphorylated in vitro by cyclin A/cdk2 and incorporation of phosphate into ER is stimulated by the ectopic expression of cyclin A in vivo. Together, these results strongly suggest a role for cyclin-dependent kinases in the regulation of ER transcriptional enhancement.

Descriptors :   *IN VITRO ANALYSIS, *IN VIVO ANALYSIS, *MAMMARY GLANDS, *ESTROGENS, *BREAST CANCER, HORMONES, MAMMALS, HUMANS, NEOPLASMS, REDUCTION, SIGNALS, YEASTS, TRANSDUCERS, CELLS(BIOLOGY), SENSE ORGANS, PHOSPHATES.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE