Evaluating the role of STAMP1 in metastatic castration-resistant prostate cancer

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Our laboratory is studying proteins that are implicated in the progression of prostate cancer (PCa); we have previously identified a number of genes that are involved in this regard. Among these genes, we are interested in analyzing the role of STAMP1, an androgen regulated six-transmembrane protein, in PCa progression. Our in vitro experiments showed that STAMP1 is critical for PCa cell growth and survival in several androgen-responsive cell lines, such as LNCaP and VCaP. Interestingly, in the castration-resistant PCa (CRPC) cell model 22Rv1, STAMP1 knockdown does not impair cell growth in vitro, but caused significant retardation of tumor growth in vivo. These results indicate that STAMP1 may have different roles in different phases of the disease, and its function may depend on the in vivo microenvironment.

Therefore, the goal of this application is to further validate these findings by utilizing another CRPC cell model, C42B, which is a metastatic derivative of LNCaP cells. We have generated stable STAMP1 knockdown C42B cell lines using two different shRNAs, neither of which caused any growth defect in vitro, consistent with our observation for 22Rv1. In this experiment, by subcutaneously inoculating the cells into nude mice, we will determine if loss of STAMP1 affects C42B xenograft growth in vivo.