title: Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration.
abstract: BACKGROUND
  The androgen receptor (AR) plays a key role in the development of prostate cancer. AR signalling mediates the expression of androgen-responsive genes, which are involved in prostate cancer development and progression. Our previous chromatin immunoprecipitation study showed that the region of abhydrolase domain containing 2 (ABHD2) includes a functional androgen receptor binding site. In this study, we demonstrated that ABHD2 is a novel androgen-responsive gene that is overexpressed in human prostate cancer tissues.
  
  
  METHODS
  The expression levels of ABHD2 in androgen-sensitive cells were evaluated by quantitative reverse transcription polymerase chain reaction and western-blot analyses. LNCaP and VCaP cells with ABHD2 overexpression or short interfering RNA (siRNA) knockdown were used for functional analyses. ABHD2 expression was examined in clinical samples of prostate cancer by immunohistochemistry.
  
  
  RESULTS
  We showed that ABHD2 expression is increased by androgen in LNCaP and VCaP cells. This androgen-induced ABHD2 expression was diminished by bicalutamide. While stable expression of ABHD2 affected the enhancement of LNCaP cell proliferation and migration, siRNA-mediated ABHD2 knockdown suppressed cell proliferation and migration. In addition, the siRNA treatment significantly repressed the tumour growth derived from LNCaP cells in athymic mice. Immunohistochemical analysis of ABHD2 expression in tumour specimens showed a positive correlation of ABHD2 immunoreactivity with high Gleason score and pathological N stage. Moreover, patients with high immunoreactivity of ABHD2 showed low cancer-specific survival rates and a resistance to docetaxel-based chemotherapy.
  
  
  CONCLUSIONS
  ABHD2 is a novel androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy, and is a novel target for diagnosis and treatment of prostate cancer.
authors: Department of Urology, Nihon University School of Medicine, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Daisuke
authors: D
authors: Obinata
authors: Department of Urology, Nihon University School of Medicine, Japan.
authors: Shogo
authors: S
authors: Takada
authors: Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan.
authors: Ken-ichi
authors: K
authors: Takayama
authors: Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan.
authors: Tomohiko
authors: T
authors: Urano
authors: Department of Urology, Nihon University School of Medicine, Japan.
authors: Akiko
authors: A
authors: Ito
authors: Department of Urology, Nihon University School of Medicine, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Daisaku
authors: D
authors: Ashikari
authors: Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Japan.
authors: Kyoko
authors: K
authors: Fujiwara
authors: Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Yuta
authors: Y
authors: Yamada
authors: Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Taro
authors: T
authors: Murata
authors: Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Jinpei
authors: J
authors: Kumagai
authors: Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Tetsuya
authors: T
authors: Fujimura
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan.
authors: Kazuhiro
authors: K
authors: Ikeda
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan.
authors: Kuniko
authors: K
authors: Horie-Inoue
authors: Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Yukio
authors: Y
authors: Homma
authors: Department of Urology, Nihon University School of Medicine, Japan.
authors: Satoru
authors: S
authors: Takahashi
authors: Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan. Electronic address: INOUE-GER@h.u-tokyo.ac.jp.
authors: Satoshi
authors: S
authors: Inoue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism; D016019:Survival Analysis; D043823:Taxoids / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D006867:Hydrolases; C525115:ABHD2 protein, human
keywords: ABHD2; Androgen receptor; Prostate cancer