Estrogen receptor α induces prosurvival autophagy in papillary thyroid cancer via stimulating reactive oxygen species and extracellular signal regulated kinases

Dahua Fan, 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

Research output: Contribution to journalArticlepeer-review

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 enhancinganimportant prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.

Original languageEnglish (US)
Pages (from-to)E561-E571
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number4
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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