Dahua Fan1, Shirley Y W Liu, C Andrew van Hasselt, Alexander C Vlantis, Enders K W Ng, Haitao Zhang, Yujuan Dong, Siu Kwan Ng, Ryan Chu, Amy B W Chan, Jing Du, Wei Wei, Xiaoling Liu, Zhimin Liu, Mingzhao Xing, George G Chen. 1. 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.
Abstract
CONTEXT: 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. DESIGN: 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.
CONTEXT: 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. DESIGN: 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: Tim Lahm; Andrea L Frump; Marjorie E Albrecht; Amanda J Fisher; Todd G Cook; Thomas J Jones; Bakhtiyor Yakubov; Jordan Whitson; Robyn K Fuchs; Aiping Liu; Naomi C Chesler; M Beth Brown Journal: Am J Physiol Lung Cell Mol Physiol Date: 2016-06-10 Impact factor: 5.464