Accession Number : ADA330258

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 96-30 Jun 97,

Corporate Author : CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s) : Kushner, Peter J.

PDF Url : ADA330258

Report Date : JUL 1997

Pagination or Media Count : 34

Abstract : Progestins and glucocorticoids are sometimes used as second line therapy for breast cancer that has become resistant to antiestrogens. We investigated whether the opposing actions of estrogens and glucocorticoids (or progestins) might reflect the opposing actions of hormone bound receptors on target genes regulated by the AP-l response element. We found that estrogens stimulate, while the glucocorticoid dexamethasone (Dex) inhibits, transcription through a model promoter from the collagenase gene (-73 to +63 bearing a consensus AP- 1 response element. Together the hormones counteracted each others effects, and the amount of transfected receptor for estrogen (ER) or glucocorticoid (GR) determined which prevailed. Dex also inhibited tamoxifen activated AP-l. Both progesterone receptor -A and -B also interacted with the ER at the A')- 1 site. These data indicate that opposing steroid influences can be mediated at the level of transcription through the A')- 1 site and suggest that the integration of hormone action at this response element may underlie some of the opposing actions of estrogens and glucocorticoids or progestins on physiologic responses.

Descriptors :   *HORMONES, *RECEPTOR SITES(PHYSIOLOGY), *PROGESTERONE, *ESTROGENS, *BREAST CANCER, IONS, ACTIVATION, TARGETS, INTEGRATION, RESPONSE, PHYSIOLOGICAL EFFECTS, THERAPY, GENES, RESPONSE(BIOLOGY), SENSE ORGANS, ANTIINFLAMMATORY AGENTS, ADRENAL CORTEX HORMONES, COLLAGENASE.

Subject Categories : Medicine and Medical Research
      Stress Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE