Genetic Construction and Molecular Characterization of Breast Cancer Precursor Cells.
Annual rept. 31 May 95-30 May 96,
UTAH UNIV SALT LAKE CITY
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The key to better understanding the cellular and molecular phenomena associated with the development of breast cancer is to reconstruct the early events in the breast carcinogenesis pathway. Mutations in genes governing cell cycle and growth regulation, such as retinoblastoma RB and p53, are expected to have a significant role in breast cancer. Both RB and p53 deficient human mammary epithelial cells HMEC were created by infecting retroviruses that express the human papilloma virus genes E6 and E7, previously shown to abrogate p53 and RB protein pRB function, respectively. Western blot analysis of these HMEC showed an absence of p53 in cells expressing E6 and a reduction of pRB in cells expressing E7. The functional activity of pRB in E7 cells is currently being examined using phosphorylation studies. E6 and E7 HMEC were investigated for growth response to TGF-B, an indicator of cellular transformation. HMEC containing just E6 or E6 and E7 were only partially growth inhibited. The ability of these cells to still grow in the presence of TGF-B indicates a significant change from the normal cellular response. It would be interesting to conduct future experiments on HMEC grown in an extracellular matrix ECM, creating a functionally relevant model system.
- Anatomy and Physiology
- Medicine and Medical Research