Beta-2-microglobulin expression correlates with high-grade prostate cancer and specific defects in androgen signaling.
BACKGROUND
Previously, we identified Beta-2-microglobulin (beta2M) as an androgen-regulated secreted protein elevated in the serum of prostate cancer patients. In this study, we explore an interaction between beta2M expression, prostate cancer tissue, and the androgen signaling axis.


METHODS
beta2M expression in relation to clinical and pathologic variables was examined in a tissue microarray representing specimens obtained at the time of radical prostatectomy. Viral vectors were designed to down-regulate beta2M expression, and the effects on androgen-dependent growth, transcriptional regulation, and androgen receptor recruitment was investigated in human prostate cancer cell lines.


RESULTS
Variation in beta2M expression in human prostate cancer is associated with characteristics of clinically aggressive disease such as high tumor grade. Knockdown of beta2M expression in human prostate cancer cells resulted in selective defects in androgen-dependent events including growth, gene regulation, and chromatin assembly.


CONCLUSIONS
beta2M expression may provide prognostic information in patients treated with surgery for prostate cancer. Targeting beta2M expression or activity may represent a new and important mechanism to manipulate the androgen signaling axis in patients with prostate cancer.
Mink
Sheldon R
SR
Louis Warschaw Prostate Cancer Center, Sumner M. Redstone Prostate Cancer Research Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Hodge
Amanda
A
Agus
David B
DB
Jain
Anjali
A
Gross
Mitchell E
ME
D000368:Aged; D000728:Androgens / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D001613:beta 2-Microglobulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
C410798:AR protein, human; D000728:Androgens; D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D001613:beta 2-Microglobulin