Role of Nuclear Receptor Coactivators, AIB-1 and SRC-1, in the Development of Breast Cancer

摘要

Steroid hormones are involved in the development and growth of breast cancer. Drugs, which inhibit estrogen action, are commonly used to inhibit breast cancer growth. Unfortunately, most advanced breast cancer becomes resistant to estrogen treatment. Recently, many steroid receptor coactivators have been discovered and found to potentiate the transcriptional activity of steroid receptors and enhance the expression of hormone response genes. In the SRC-l family of coactivators, AIBl is found amplified and/or over-expressed in breast cancer specimens. To evaluate the potential roles of the SRC-1 family of coactivators in mammary tumorigenesis in vivo, we proposed to generate transgenic mice over-expression of AIB1 (SRC-3) in mammary glands. To target the expression of AIB1 in mammary gland, we placed the AIB1 transgene under the control of the MMTV-LTP promoter. Two lines of transgenic mice expressing AIBl have been generated. Studies on these transgenic mice will help understand the development and progression of breast cancer and provide a molecular basis for designing novel strategies to curb and, ultimately, cure breast cancer.