The Role of Steroid Receptor Coactivator-1 in Breat Cancer
Abstract
The steroid hormones estrogen and progesterone and their intracellular receptors, ER and PR, have been implicated in the development and progression of primary epithelial breast cancer. Regulation of gene expression by liganded steroid receptors is mediated by members of the steroid receptor coactivator (SRC-1) family, which are required by steroid receptors for efficient transcriptional regulation. Targeted deletion of SRC-1 in our laboratory suggests that it is required for hormone-stimulated proliferation of the mammary gland, implicating SRC-1 as a potential therapeutic target in breast cancer. For this reason we set out to examine the molecular role of SRC-1 in breast cancer. Using the liganded PR as a bait in a biochemical interaction assay, we identified an SRC-1 containing complex from cancer cell nuclear extracts. This complex was recruited by human PR in a ligand-dependent manner to acetylate core histones, a step thought to be a key event in the activation of steroid-regulated genes. We are currently identifying other members of this active SRC-1 complex. We suggest that SRC-1 and SRA function in breast cancer as a member of a large muitiprotein complex which is recruited stably by liganded steroid receptors for efficient transcriptional regulation, and that members of the active SRC-1 complex are potential therapeutic targets in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADB266221
Entities
People
- Neil Mckenna
Organizations
- Baylor College of Medicine