Accession Number : ADA322220

Title :   Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 or BRCAl Genes.

Descriptive Note : Annual rept. 22 Sep 95-21 Sep 96,

Corporate Author : UTAH UNIV SALT LAKE CITY

Personal Author(s) : White, Raymond L.

PDF Url : ADA322220

Report Date : OCT 1996

Pagination or Media Count : 32

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.

Descriptors :   *EPITHELIUM, *MUTATIONS, *GENES, *BREAST CANCER, HUMANS, ENZYMES, NEOPLASMS, TRANSDUCERS, CELLS(BIOLOGY), GENETICS, TRANSFORMATIONS, MAMMARY GLANDS, SUPPRESSORS.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE