Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 or BRCAl Genes.
Abstract
During the second year of the funding period, we created human mammary epithelial cells (HMEC) with altered p53 or Rb activity by transducing human papillomavirus type 16 (HPV16) E6 or E7 gene, and examined them for known indicators of cellular immortalization and transformation, such as telomerase activation and response to TGF-beta. In particular, we have demonstrated that early- and late-passages of HMEC contain different population of cell types showing remarkably different susceptibilities to E6 and E7, which target p53 and Rb functions, respectively. The difference is evident not only for immortalization of transduced cells but also for activation of telomerase during pre-crisis, that is prior to immortalization. This finding may provide clues to the roles of different oncogenes, tumor suppressor genes, and telomerase in the process of transformation of distinct types of breast cells. Experiments using pure populations of luminal and basal HMEC may provide direct insights into these mechanisms. We also describe the evidence that expression status of bcl-2 may contribute to mammary tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADA322220
Entities
People
- Raymond L. White
Organizations
- University of Utah