MECHANISMS OF PROSTATE EPITHELIAL CELL TRANSFORMATION

描述：本提案的总体目标是确定

DESCRIPTION: The overall objective of this proposal is to identify molecular genetic mechanisms by which adult human non-neoplastic prostate epithelial cells are driven towards increasingly malignant phenotypes. Investigation of specific cytogenetic alterations found to be associated with the tumorigenic or metastatic capacity of SV40 large T antigen immortalized human prostate epithelial cells (SV40T PEC) in athymic nude mice provides a novel way to study mechanism of transformation. In this proposal, the hypothesis to be tested is that chromosomes 16 and/or 19 contain one or more genes that suppress tumorigenicity and/or metastasis. The specific aims are: (1) to further delineate the minimal regions of loss of heterozygosity (LOH) occurring on chromosomes 16 and 19 as these cells progress; (2) to determine whether restoration of normal chromosome dosage by microcell mediated transfer of: (a) an intact normal human chromosome 16, or (b) chromosome 19 into appropriate clones will suppress tumor incidence, growth rate, and/or metastasis in athymic nude mice; (3) to exploit their unique system to identify the smallest areas on chromosomes 16 and/or 19 that harbor functional tumor suppressor activity. These studies will facilitate understanding of the most common tumor occurring among American men. This may lead to new opportunities for improved diagnosis, prognostic assessment, or therapeutic intervention for a disease having no satisfactory treatment options.