title: The role of DAB2IP in androgen receptor activation during prostate cancer progression.
abstract: Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP(-/-) mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.
authors.affiliation: 1] Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA [2] Department of Urology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX, USA.
authors.forename: S-F
authors.initials: SF
authors.lastname: Tseng
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gore
authors.affiliation: Department of Urology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sharifi
authors.affiliation: Vancouver Prostate Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Vancouver Prostate Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Gleave
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: O K
authors.initials: OK
authors.lastname: Oz
authors.affiliation: Interdepartmental Program in Vascular Biology and Transplantation and Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: W
authors.initials: W
authors.lastname: Min
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alexandrakis
authors.affiliation: Department of Urology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: C-R
authors.initials: CR
authors.lastname: Yang
authors.affiliation: 1] Graduate Institute of Cancer Biology, China Medical University Hospital, Taichung, Taiwan [2] Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan [3] Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: C-L
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: 1] Department of Urology, China Medical University Hospital, Taichung, Taiwan [2] School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: H-C
authors.initials: HC
authors.lastname: Wu
authors.affiliation: Department of Urology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: D
authors.initials: D
authors.lastname: He
authors.affiliation: Department of General Surgery, Tongji Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: D
authors.initials: D
authors.lastname: Xie
authors.affiliation: 1] Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA [2] Graduate Institute of Cancer Biology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: J-T
authors.initials: JT
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: C462952:DAB2IP protein, human; C561450:Dab2ip protein, mouse; D011944:Receptors, Androgen; D020703:ras GTPase-Activating Proteins