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Calcitonin (CT) and its receptor (CTR) are expressed in basal epithelium of benign prostate but whole epithelium of malignant prostates. The abundance of CT and CTR mRNA in prostate cancers increases with increase in tumor grade and all tumor cells of poorly differentiated prostate cancers co-express CT/CTR.

Using CTR-positive PC-3M and CTR-deficient PC-3 cells as models, we tested the hypothesis that the expression and activation of CTR plays an important role in tumorigenicity of prostate cancer cells. We enforced CTR expression in PC-3 cells and silenced it in PC-3M cells. The effect of these modulations on oncogenicity of the cell lines was evaluated by cell proliferation, invasion and colony formation assays and in vivo growth in athymic nude mice. We also administered CTR siRNA plasmid intratumorally in preexisting tumors in nude mice, and examined its impact on further tumor growth. The harvested tumors were evaluated for CTR-activated signaling events.

Our results suggest that the enforced expression of CTR in PC-3 cells dramatically enhanced their oncogenicity. In contrast, the silencing of CTR expression in PC-3M cells markedly reduced their oncogenicity. In vivo silencing of CTR expression in preexisting PC-3M xenografts led to their growth arrest and a large increase in apoptotic cell populations. These results, when combined with our results that all tumor cells of invasive prostate cancers co-express CT/CTR, support a possibility that the activation of CT-CTR axis plays an important role in the progression of PC from a localized tumor to a metastatic phenotype.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA