STAMP1 Is Both a Proliferative and an Antiapoptotic Factor in Prostate Cancer

Abstract

STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and is deregulated in prostate cancer. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, is unknown. Here, we find that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS-7 cells in vitro; conversely, small interfering RNA-mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth and, at least partially, induced cell cycle arrest. In parallel, there were alterations in cell cycle-regulatory gene expression. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. Consistently, LNCaP cells with short hairpin RNA-mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Interestingly, activation of extracellular signal-regulated kinase, which has previously been implicated in prostate cancer progression, was significantly increased on ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly downregulated on STAMP1 knockdown in LNCaP cells. In the normal prostate, STAMP1 protein is localized to the cytosol and the cell membrane of the prostate epithelial cells; furthermore, its expression is increased in prostate cancer compared with normal prostate. Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment. Cancer Res; 70(14); 5818-28. ©2010 AACR.

STEAP Proteins: From Structure to Applications in Cancer Therapy

“…In situ hybridization analysis of 18 normal and 25 tumoral prostate sections showed that STEAP2 expression is about 2.5-fold higher in prostate cancer cells than in normal cells, suggesting that STEAP2 could be implicated in prostate cancer progression (7). Moreover, the immunohistochemical analysis of 17 benign and 67 cancer specimens of prostate tissue was in agreement with mRNA expression data (27). Despite the higher levels of STEAP2 mRNA and protein in prostate cancer, the only study that attempted to establish an association of STEAP2 expression with the Gleason score of prostate tumors was unsuccessful (27).…”

“…Moreover, the immunohistochemical analysis of 17 benign and 67 cancer specimens of prostate tissue was in agreement with mRNA expression data (27). Despite the higher levels of STEAP2 mRNA and protein in prostate cancer, the only study that attempted to establish an association of STEAP2 expression with the Gleason score of prostate tumors was unsuccessful (27). However, this question should be further analyzed as the expression of ERK, 1 of the proteins that may mediate the proliferative and antiapoptotic functions of STEAP2, augments from normal to benign prostate hyperplasia and prostate cancer stages (27).…”

“…Despite the higher levels of STEAP2 mRNA and protein in prostate cancer, the only study that attempted to establish an association of STEAP2 expression with the Gleason score of prostate tumors was unsuccessful (27). However, this question should be further analyzed as the expression of ERK, 1 of the proteins that may mediate the proliferative and antiapoptotic functions of STEAP2, augments from normal to benign prostate hyperplasia and prostate cancer stages (27). If ERK expression is associated with advanced stages of prostate cancer and mediates STEAP2 functions, is STEAP2 expression really independent of the tumor grade?…”

Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer

“…Apoptosis and the treatments for its induction and detection were as described previously (55). To detect proapoptotic factorinduced apoptosis, cells were treated with 50 ng/mL TRAIL (Enzo Life Sciences), 20 μM LY294002 (Invitrogen), or a combination of both agents for indicated times.…”

Role of Six Trans Membrane Protein of Prostate (STAMP) Proteins in Prostate Cancer- Relation with Survival Genes

“…Activation of extracellular signal-regulated kinase (ERK), which has previously been implicated in prostate cancer progression, was reported with ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly down regulated on STAMP1 knockdown in LNCaP cells [7]. Promoter region of the STAMP genes were analyzed and putative presence of tumor suppressor gene p53 and survival gene NFkB response elements were identified and confirmed at the promoter region of STAMP1 and STAMP2 genes [8].…”