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.
Tamura
Kenji
K
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Furihata
Mutsuo
M
Chung
Su-Yong
SY
Uemura
Motohide
M
Yoshioka
Hiroki
H
Iiyama
Tatsuo
T
Ashida
Shingo
S
Nasu
Yasutomo
Y
Fujioka
Tomoaki
T
Shuin
Taro
T
Nakamura
Yusuke
Y
Nakagawa
Hidewaki
H
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
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human