Prostate cancer is the most common non-cutaneous cancer among men and is the second leading cause of cancer deaths in men in Western countries. The specific cause(s) of prostate cancer progression is still unknown. An approach to address this question is to find genes that are prostate enriched and differentially expressed during cancer progression. Recent studies have identified a number of candidate genes whose products may be involved in prostate cancer development and which may therefore be used as markers, as well as therapeutic targets, for prostate cancer. One of these genes is Six Transmembrane Protein of Prostate 1 (STAMP1) identified in our laboratory several years ago. STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and we had previously shown that it is deregulated in prostate cancer at the mRNA level. STAMP1 expression is androgen independent, but mainly occurs in androgen receptor (AR) positive cells. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, has been unknown. The aim of this study was to examine the possible role of STAMP1 in prostate cancer biology in vitro and in vivo.

We found that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS7 cells in vitro; conversely, siRNA-mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth, and at least in part, induced cell cycle arrest, evidenced by up-regulation of the cell cycle inhibitor p21. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to Tumor Necrosis Factor (TNF) Related Apoptosis Inducing Ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. This suggests that STAMP1 is a survival factor in prostate cancer and its knockdown could be useful in the clinic in combination with other treatment modalities. Consistently, LNCaP cells with shRNA mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Furthermore, in the prostate cancer cell line DU145 ectopic expression of STAMP1 increased Extracellular Signal Regulated Kinase (ERK) activity induced by Epidermal Growth Factor (EGF) whereas STAMP1 knockdown in LNCaP cells significantly impaired ERK activation. These results, coupled to previous findings implicating EGF and ERK signaling in prostate carcinogenesis, suggest that the proliferative and antiapoptotic activities of STAMP1 may be mediated by ERK signaling.

Immunohistochemical staining of prostate tissue specimens showed that STAMP1 protein is localized to the cytosol and the cell membrane of prostate epithelial cells in the normal prostate. Analysis of a tissue microarray encompassing 17 normal and 67 prostate cancer cases showed that STAMP1 expression is increased in prostate cancer compared with normal prostate.

In summary, these data show that STAMP1 is involved in a signaling pathway that is linked to cell cycle progression as well as inhibition of apoptosis in prostate cancer cells. These data suggest that STAMP1 may play important roles in prostate cancer development and progression and thus may prove to be a useful target in prostate cancer therapy.

Yang Jin, Ling Wang, and Fahri Saatcioglu as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

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