Characterization and expression analysis of STAMP1 isoforms in prostate cancer

Abstract

Prostate cancer (PCa) is the most common type of cancer among men in Western countries. An approach to better PCa diagnosis, prognosis and management is to identify genes that are prostate-specific and differentially expressed during cancer progression. One such a candidate gene is six-transmembrane protein of prostate 1 (STAMP1), which is upregulated in prostate tumors, promote proliferation and inhibit apoptosis of PCa cells. STAMP1 is required for PCa growth and may thus serve as a potential diagnostic, prognostic marker or a therapeutic target. Six mRNA transcripts of STAMP1 have been reported, potentially encoding three different protein isoforms (STAMP1-490, -454, -419), which have not been characterized to date. In this thesis we investigated expression patterns of all STAMP1 mRNA isoforms in various human tissues, PCa cells and human prostate specimens collected from patients with benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and PCa. We show that all STAMP1 isoforms are highly prostate-enriched. Furthermore, STAMP1-454 was overexpressed in PIN samples, compared to BPH and PCa samples and elevated STAMP1-490 expression was associated with higher tumor stage in PCa specimens. Interestingly, STAMP1-454 and STAMP1-419 mRNA expression was induced by androgens in LNCaP, VCaP, and 22Rv1 cell lines, whereas STAMP1-490 expression was not regulated by androgens at either mRNA or protein levels. We suggest that androgens regulate STAMP1 isoform expression at the level of transcription and in large part do not require de novo protein synthesis. Moreover, we demonstrate that active AR is necessary for STAMP1 isoform expression, since AR knockdown decreased mRNA levels of all three STAMP1 isoforms. In addition, our results show that STAMP1 is required for optimum AR signaling, which is one of the major pathways implicated in PCa. These data suggest that STAMP1 isoforms may have important differential functions in PCa biology.