Accession Number : ADA332673

Title :   Hormone Resistance and Progesterone Receptors in Breast Cancer.

Descriptive Note : Annual rept. 15 Jun 96-14 Jun 97

Corporate Author : COLORADO UNIV HEALTH SCIENCES CENTER DENVER

Personal Author(s) : Horwitz, Kathryn B.

PDF Url : ADA332673

Report Date : JUL 1997

Pagination or Media Count : 76

Abstract : The overall goal of the proposed research has been to understand the mechanisms by which breast cancers become resistant to hormone treatments. Specifically, the hormones involved are the steroidal agonists, estradiol and progesterone, the antagonists tamoxifen and RU-486, and the receptors to which these hormones bind, namely estrogen (ER) and progesterone receptors (PR). To this end, we initially used as models the PR of human breast cancer cells and the antiprogestin RU-486. We anticipated that the mechanisms we uncovered for progestins would be relevant to estrogens as well. This has turned out to be the case. We have discovered two proteins, which interact with antagonist-occupied receptors, and alter the direction of receptor-dependent transcription. (1) We isolated a coactivator, which we have dubbed L7/SPA, that interacts with tamoxifen-occupied ER or RU-486 occupied PR and increases transcription by 3-10 fold. It does not enhance agonist-dependent transcription, however. (2) We also isolated a corepressor protein that suppresses the partial agonist activity of tamoxifen or RU-486. These proteins may enhance (L7/SPA) or inhibit (corepressor) development of hormone resistant breast cancers, and this is now being tested in tumors taken from patients.

Descriptors :   *RECEPTOR SITES(PHYSIOLOGY), *RESISTANCE(BIOLOGY), *PROGESTERONE, *BREAST CANCER, HORMONES, HUMANS, PROTEINS, CELLS(BIOLOGY), ESTROGENS.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE