Gene Activation by Antiestrogens Used in Breast Cancer Therapy via the Interaction of Estrogen Receptor and AP-1.
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA330258
Entities
People
- Peter J. Kushner
Organizations
- University of California, San Francisco