Dr. Jeng's laboratory is interested in the hormonal actions and roles of steroid receptor coregulators in normal and neoplastic breast tissue. Overexpression of estrogen receptor a (ERa) transcriptional coregulators, such as AIB1 (coactivator amplified in breast cancer-1), has been demonstrated in many ERa-positive human breast and ovarian cancer cell lines and tumors. These transcriptional coactivators, including members of the steroid receptor coactivator-1 family (SRC-1, GRIP1/TIF1/SRC-2, c/CIP/AIB1/SRC-3) and coactivator-associated arginine methyltransferase 1 (CARM1) can potentiate the estrogen-induced transcriptional activation of ERa target genes. Interestingly, Dr. Jeng's group has found that SRC-1 was segregated from ERa and progesterone receptor in virgin female mammary epithelium. These results raise the possibility that SRC-1 family members may have cell- and tissue-specific functions and that altered expression of steroid receptor coregulators can potentiate the transcriptional activities of ERa and subsequently contribute to estrogen-stimulated cancer cell proliferation. Her group has focused on the following research areas: 1) dissecting the roles of SRC-1 family members and other coregulators in ER transactivation, cell proliferation, and tumorigenesis in breast tissue, using molecular biology, biochemical, and adenoviral approaches; 2) determining the cell- and tissue-specific actions of SRC-1 family members; and 3) investigating the roles of CARM1 in mitogenesis and apoptosis in breast cancer. They also have demonstrated that both MAP kinase-dependent and MAP kinase-independent pathways are involved in the transactivation function of ER and the enhanced cell proliferation of long term estrogen-deprived human breast cancer cells. Studies are ongoing to examine the signaling pathways that regulate the activities of MAP kinase in hormone refractory human breast cancer cells. Better understanding of the mechanisms of steroid receptor coregulator actions may lead to the development of new therapeutic targets and improved strategies for the prevention and treatment of breast cancer. breast cancer, hormone actions
The laboratory is focused on understanding the mechanism of action of steroid hormones during normal breast development and breast cancer progression in order to identify potential molecular targets for breast cancer treatment.
Breast Cancer
