Role of opiorphin genes in prostate cancer growth and progression

BACKGROUND: We describe the first studies investigating a role for opiorphin genes (PROL1, SMR3A and SMR3B) in prostate cancer (PrCa). MATERIALS & METHODS: Databases and PrCa tissue arrays were screened for opiorphin expression. Xenografted tumor growth of human PrCa cells overexpressing PROL1 was compared with controls in nude mice. Modulated gene expression by overexpression of PROL1 was determined by RNA sequencing. RESULTS: PrCa is associated with overexpression of opiorphin genes. Xenografted androgen-sensitive PrCa cells overexpressing PROL1 developed into tumors in castrated male mice (in contrast to parental cells). PROL1 overexpression modulates expression of genes in angiogenesis, steroid and hypoxic response pathways. CONCLUSIONS: Opiorphins promote the development of androgen-insensitive PrCa and activate pathways that potentially overcome the hypoxic barrier generated during tumor growth.