title: Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.
abstract: Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea; Drug Discovery Center, JW Pharmaceutical Co, Seoul 137-864, Korea;
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Cha
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea;
authors.forename: Jungwon
authors.initials: J
authors.lastname: Wee
authors.affiliation: Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Jung
authors.affiliation: Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea;
authors.forename: Byeongjun
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea;
authors.forename: Gyu-Sang
authors.initials: GS
authors.lastname: Hong
authors.affiliation: Drug Discovery Center, JW Pharmaceutical Co, Seoul 137-864, Korea;
authors.forename: Beom Chul
authors.initials: BC
authors.lastname: Chang
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea;
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Min
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Na
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Mi-Ock
authors.initials: MO
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea; Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151-742, Korea; utoh@snu.ac.kr.
authors.forename: Uhtaek
authors.initials: U
authors.lastname: Oh
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018118:Chloride Channels / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D013196:Dihydrotestosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D006965:Hyperplasia; D007267:Injections; D015640:Ion Channel Gating / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D017208:Rats, Wistar; D020218:Response Elements / Q000235:genetics; D013634:Tannins / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C476213:ANO1 protein, human; C552942:ANO1 protein, rat; D000075369:Anoctamin-1; D015220:Calcium Channels; D018118:Chloride Channels; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D013634:Tannins; D013196:Dihydrotestosterone; D013739:Testosterone; D008156:Luciferases; D002118:Calcium
keywords: anoctamin 1; hyperplasia; proliferation; prostate; testosterone