PMID- 21546410
OWN - NLM
STAT- MEDLINE
DCOM- 20111014
LR  - 20211020
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 25
IP  - 7
DP  - 2011 Jul
TI  - Activation of the signal transducer and activator of transcription 3 pathway 
      up-regulates estrogen receptor-beta expression in lung adenocarcinoma cells.
PG  - 1145-58
LID - 10.1210/me.2010-0495 [doi]
AB  - Estrogens contribute to the pathogenesis of female lung cancer and function 
      mainly through estrogen receptor-beta (ERbeta). However, the way in which ERbeta 
      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 ERbeta 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 ERbeta mRNA and protein expression in lung 
      cancer cells. The induction of ERbeta in 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 ERbeta 
      promoter. Besides the Janus kinase 2/Stat3 pathway, the MEK/Erk pathway 
      contributes to ERbeta up-regulation induced by 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 ERbeta expression in lung cancer cells. Inhibiting Stat3 activity by 
      pharmacological or genetic approaches reduced EGF- and L858R mutant EGFR-induced 
      ERbeta expression, indicating that Stat3 activation is required for EGFR 
      signaling-mediated ERbeta up-regulation. Silencing ERbeta decreased cell proliferation 
      in lung cancer cells that overexpress L858R mutant EGFR. In conclusion, we have 
      identified that Stat3 activation is essential for ERbeta induction by IL-6, EGF, and 
      the presence of EGFR mutation. The findings shed light on new therapeutic targets 
      for female lung cancer, especially for those with EGFR mutations.
FAU - Wang, Hao-Chen
AU  - Wang HC
AD  - Institute of Basic Medical Sciences, National Cheng Kung University, Medical 
      College, Tainan, Taiwan, Republic of China.
FAU - Yeh, Hsuan-Heng
AU  - Yeh HH
FAU - Huang, Wei-Lun
AU  - Huang WL
FAU - Lin, Chien-Chung
AU  - Lin CC
FAU - Su, Wen-Pin
AU  - Su WP
FAU - Chen, Helen H W
AU  - Chen HH
FAU - Lai, Wu-Wei
AU  - Lai WW
FAU - Su, Wu-Chou
AU  - Su WC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110505
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adenocarcinoma
MH  - Adenocarcinoma of Lung
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Epidermal Growth Factor/pharmacology/physiology
MH  - ErbB Receptors/genetics/metabolism
MH  - Estrogen Receptor beta/genetics/*metabolism
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Interleukin-6/pharmacology/physiology
MH  - Lung Neoplasms
MH  - *MAP Kinase Signaling System
MH  - Mutation, Missense
MH  - Neoplasms, Hormone-Dependent
MH  - Phosphorylation
MH  - Protein Binding
MH  - RNA Stability
MH  - STAT3 Transcription Factor/*metabolism
MH  - Transcription, Genetic
MH  - *Up-Regulation
PMC - PMC5417244
EDAT- 2011/05/07 06:00
MHDA- 2011/10/15 06:00
PMCR- 2012/07/01
CRDT- 2011/05/07 06:00
PHST- 2011/05/07 06:00 [entrez]
PHST- 2011/05/07 06:00 [pubmed]
PHST- 2011/10/15 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - me.2010-0495 [pii]
AID - me-10-0495 [pii]
AID - 10.1210/me.2010-0495 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2011 Jul;25(7):1145-58. doi: 10.1210/me.2010-0495. Epub 2011 May 
      5.