title: Estrogen receptor α induces prosurvival autophagy in papillary thyroid cancer via stimulating reactive oxygen species and extracellular signal regulated kinases.
abstract: BACKGROUND
  The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown.
  
  
  OBJECTIVE
  This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC.
  
  
  METHODS
  The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed.
  
  
  RESULTS
  ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC.
  
  
  CONCLUSIONS
  ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.
authors.affiliation: Departments of Otorhinolaryngology, Head and Neck Surgery (D.F., C.A.v.H., A.C.V., S.K.N., R.C.), Surgery (S.Y.W.L., E.K.W.N., Y.D., G.G.C.), and Anatomical and Cellular Pathology (A.B.W.C.), The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China; Department of Biochemistry and Molecular Biology (H.Z.), Guangdong Medical College, Zhanjiang, Guangdong, 524023 China; Peking University Shenzhen Hospital (J.D., W.W., X.L.), Shenzhen, Guangdong, China 518036; Department of Biochemistry and Molecular Biology (Z.L.), Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, China 40016; and Division of Endocrinology, Diabetes, and Metabolism (M.X.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218.
authors.forename: Dahua
authors.initials: D
authors.lastname: Fan
authors.forename: Shirley Y W
authors.initials: SY
authors.lastname: Liu
authors.forename: C Andrew
authors.initials: CA
authors.lastname: van Hasselt
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Vlantis
authors.forename: Enders K W
authors.initials: EK
authors.lastname: Ng
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Dong
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Ng
authors.forename: Ryan
authors.initials: R
authors.lastname: Chu
authors.forename: Amy B W
authors.initials: AB
authors.lastname: Chan
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D017382:Reactive Oxygen Species; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases