title: Beta2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells.
abstract: OBJECTIVE
  beta2-Microglobulin (beta2M) has been shown to promote osteomimicry and the proliferation of human prostate cancer cells. The objective of this study is to determine the mechanism by which targeting beta2M using anti-beta2M antibody inhibited growth and induced apoptosis in prostate cancer cells.
  
  
  METHODS
  Polyclonal and monoclonal beta2M antibodies were used to interrupt beta2M signaling in human prostate cancer cell lines and the growth of prostate tumors in mice. The effects of the beta2M antibody on a survival factor, androgen receptor (AR), and its target gene, prostate-specific antigen (PSA) expression, were investigated in cultured cells and in tumor xenografts.
  
  
  RESULTS
  The beta2M antibody inhibited growth and promoted apoptosis in both AR-positive and PSA-positive, and AR-negative and PSA-negative, prostate cancer cells via the down-regulation of the AR in AR-positive prostate cancer cells and directly caused apoptosis in AR-negative prostate cancer cells in vitro and in tumor xenografts. The beta2M antibody had no effect on AR expression or the growth of normal prostate cells.
  
  
  CONCLUSIONS
  beta2M downstream signaling regulates AR and PSA expression directly in AR-positive prostate cancer cells. In both AR-positive and AR-negative prostate cancer cells, interrupting beta2M signaling with the beta2M antibody inhibited cancer cell growth and induced its apoptosis. The beta2M antibody is a novel and promising therapeutic agent for the treatment of human prostate cancers.
authors.affiliation: Molecular Urology and Therapeutics Program, Department of Urology and Winship Cancer Institute, Emory University School of Medicine, GA 30322, USA. whuang3@emory.edu
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Huang
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Havel
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Wei Ping
authors.initials: WP
authors.lastname: Qian
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Lue
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Chu
authors.forename: Takeo
authors.initials: T
authors.lastname: Nomura
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung