Gene Targets in Prostate Tumor Cells that Mediate Aberrant Growth and Invasiveness
Annual rept. 1 Feb 2002-31 Jan 2002
BURNHAM INST LA JOLLA CA
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Overall, this study is based on the hypothesis that the human PPC-1 prostate tumor cell line with experimentally altered Ets transcription factor function, which show a reduction in the transformed phenotype, do so because of altered expression patterns in important genes downstream of Ets factors. We proposed to analyze global differences in gene expression between these cell lines, and assess the functional significance of the observed changes in gene expression. Using xenograft studies, we have now demonstrated that the prostate tumor cells with altered Ets function exhibited a significantly reduced ability to form tumors, strengthening the biological relevance of this prostate tumor cell line system. The broad microarray analysis of altered gene expression has identified over 20 genes whose differential expression in the altered PPC-1 cells was confirmed by quantitative POR. These target genes are associated with the regulation of several important aspects of cancer cell behavior. Functional analysis of IL-B, a regulated Ets target gene we identified, indicated that its downregulation may reduce tumor cell motility. The ongoing characterization of changes in gene expression leading to reversal of prostate cell transformation, should provide important insight on the molecular basis of aggressive prostate tumor cell behavior.
- Anatomy and Physiology
- Medicine and Medical Research