Stanniocalcin 2 overexpression in castration‐resistant prostate cancer and aggressive prostate cancer

Prostate cancer is usually androgen‐dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration‐resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration‐resistant prostate cancers, we previously analyzed gene expression profiles by genome‐wide cDNA microarrays combined with microdissection and found dozens of trans ‐activated genes in clinical castration‐resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration‐resistant prostate cancer cells. Real‐time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302‐amino‐acid glycoprotein hormone, specifically in castration‐resistant prostate cancer cells and aggressive castration‐naïve prostate cancers with high Gleason scores (8–10). The gene was not expressed in normal prostate, nor in most indolent castration‐naïve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration‐resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. ( Cancer Sci 2009; 100: 914–919)