Methylation of Select Tumor Suppressor Genes in Sporadic Breast Cancer.

摘要

Breast cancer is the most frequently diagnosed cancer in American women and the second most frequent cause of cancer death. Breast cancer growth is regulated by estrogen. Estrogen receptor (FR) status is used to predict prognosis and to determine which patients will benefit from antihormonal therapy. Tamoxifen is the most commonly used antiestrogenic agent. Its long-term use leads to tumor resistance. This has led investigators to search for antiestrogens that can be used as second-line therapy for patients who develop tamoxifen resistant tumors. This proposal investigates the effectiveness of rapamycin as an antiestrogenic agent. Four specific aims are described: 1) Flow cytometry was used to show that rapamycin can inhibit the estrogen-induced cell cycle progression of ER+ breast cancer cells. 2) Rapamycin was found to inhibit estrogen-mediated transcription in ER+ breast cancer cells which had been transiently transfected with the artificial construct 3XERE-TATA-Luc. 3) Since rapamycin could potentially be used clinically its efficacy at inhibiting estrogen-dependent breast cancer growth in a mouse xenograft tumor model is currently being tested. 4) Some cytotoxic agents are also antiangiogenic. Three different assays; a cellular migration assay, an aortic ring assay and a corneal pocket assay are being developed to determine if rapamycin has any antiangiogenic effects.