Gene Targets in Prostate Tumor Cells That Mediate Aberrant Growth and Invasiveness
Annual rept. 1 Feb 2003-31 Jan 2004
BURNHAM INST LA JOLLA CA
Pagination or Media Count:
Our hypothesis that the human PPC-1 prostate tumor cell lines 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 changes in gene expression. Altered Ets function was found to delay xenograft tumor onset, and tumors from Ets2 overexpressing cells had dramatically reduced tumor microvasculature. Expanded microarray expression analysis has now identified over 65 potential Ets target genes in PPC-1 cells, including genes whose products can contribute to the observed changes in motility, invasiveness, survival, tumorigenicity, and tumor angiogenesis. Regulation of Ets target gene expression in prostate tumor cells was quite different than in other cell types, and prostate Ets family expression relative to other tissues was characterized. Follow-up analysis of Ets target genes has implicated IL-B in cell motility, PKC delta in survival, CC3 in tumor angiogenesis, and MT-MMP-1 in invasiveness. The ongoing characterization of Ets factor signaling and targets in prostate cell transformation should provide important insights on the molecular basis of aggressive prostate tumor cell behavior.
- Medicine and Medical Research