title: Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer.
abstract: 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.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Su-Yong
authors.initials: SY
authors.lastname: Chung
authors.forename: Motohide
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Iiyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Ashida
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D002369:Castration; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human