Activation of the signal transducer and activator of transcription 3 pathway Up-regulates estrogen receptor-β expression in lung adenocarcinoma cells

研究成果: Article

13 引文 斯高帕斯(Scopus)

摘要

Estrogens contribute to the pathogenesis of female lung cancer and function mainly through estrogen receptor-β (ERβ). However, the way in which ERβ expression is regulated in lung cancer cells remains to be explored. We have found that signal transducer and activator of transcription 3 (Stat3) activation up-regulates ERβ expression in PC14PE6/AS2 lung cancer cells in a preliminary Affymetrix oligonucleotide array study, and we sought to confirm the findings. In this study, we show that IL-6 induced ERβ mRNAand protein expression in lung cancer cells. The induction of ERβin response to IL-6 was abolished by Janus kinase 2 inhibitor-AG490, dominant-negative mutant of Stat3, and Stat3-targeting short interfering RNA. The luciferase reporter assay and chromatin immunoprecipitation assay confirmed that IL-6-activated Stat3 binds to the ER promoter. Besides the Janus kinase 2/Stat3 pathway, the MEK/Erk pathway contributes to ERβ up-regulation inducedby IL-6; however, the phosphoinositide -3'kinase/Akt pathway does not. We also found that epidermal growth factor (EGF) stimulation or L858R mutation in EGF receptor (EGFR) induced Stat3 activation as well as ERβ expression in lung cancer cells. Inhibiting Stat3 activity by pharmacological or genetic approaches reduced EGF- and L858R mutant EGFR-induced ERβ expression, indicating that Stat3 activation is required for EGFR signaling-mediated ERβ up-regulation. Silencing ERβ decreased cell proliferation in lung cancer cells that overexpress L858R mutant EGFR. In conclusion, we have identified that Stat3 activation is essential for ERβ induction by IL-6, EGF, and the presence of EGFR mutation. The findings shed lightonnewtherapeutic targets for female lung cancer, especially for those with EGFR mutations.

原文English
頁(從 - 到)1145-1158
頁數14
期刊Molecular Endocrinology
25
發行號7
DOIs
出版狀態Published - 2011 七月 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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