Role of c-Myc in Estrogen Stimulated Cell Proliferation in Normal and Malignant Breast Epithelial Cells
Abstract
This project focuses on the role of c-Myc in mediating estrogen actions in breast epithelial cells, specifically to determine the contribution of c-Myc to downstream molecular and cellular events after estrogen stimulation. The rationale for this investigation is, 1) the established intrinsic role of estrogens in mammary gland development and etiology of breast cancer and the proven therapeutic efficacy of antiestrogens in breast cancer, and 2) compelling evidence that has implicated the cell cycle regulatory molecules c-Myc and cyclin D1 in estrogen-induced mitogenesis. Our experimental approach involves ectopic expression of wild-type, mutant and dominant-negative variants of c-Myc to modulate c-Myc function and assay the necessity for various functional domains of c-Myc in mediating estrogen stimulation of breast cancer cell proliferation. To date, good progress has been made. An excellent model has facilitated observation of molecular events downstream from estrogen and/or c-Myc in breast cancer cells: induction of various cell cycle regulatory proteins, formation and activation of regulatory protein kinase complexes, phosphorylation of crucial target substrates and S phase progression have been documented and characterized, resulting in a high quality publication. Future work includes completion of these initial studies, extension of in vitro studies to identify functional domains of c-Myc required for its estrogen-mediating effects and ultimately, in vivo studies in reconstituted murine mammary epithelial glands
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA384059
Entities
People
- Eileen M. Rogan
Organizations
- Garvan Institute of Medical Research