Document Detail

Estrogen receptor beta (ERbeta) subtype-specific ligands increase transcription, p44/p42 mitogen activated protein kinase (MAPK) activation and growth in human non-small cell lung cancer cells.
MedLine Citation:
PMID:  19460433     Owner:  NLM     Status:  MEDLINE    
In non-small cell lung cancer (NSCLC) cells, 17beta-estradiol increases transcription, activates MAPK, and stimulates proliferation. We hypothesize that estrogen receptor beta (ERbeta) mediates these responses because it, but not ERalpha, is detected in our NSCLC cell lines. To test this, we determined the effects of the ERbeta-selective agonists genistein (GEN) and 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) and the ERalpha-selective agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) in 201T cells. The cells were transfected with either an ERalpha or an ERbeta expression vector and an estrogen response element (ERE)-tk-luciferase reporter construct. PPT increased luciferase activity in cells expressing ERalpha but not ERbeta. GEN and DPN selectively increased luciferase activity in ERbeta-transfected cells at concentrations < or =10 nM. Fulvestrant blocked the GEN- and DPN-mediated increases, indicating that transcription was ER-dependent. GEN but not PPT mediated a significant 1.5-fold increase in reporter activity upon transfection with ERE-tk-luciferase alone, demonstrating that endogenous ERbeta activates transcription. PPT and DPN increased MAPK phosphorylation (2.5-fold and 3.7-fold, respectively). However, only DPN stimulated 201T growth in vitro (p=0.008) and in vivo (p=0.05). We conclude that ERbeta mediates genomic and non-genomic responses to estrogen in 201T cells and that activation of both pathways may be necessary for increased proliferation of these cells.
Pamela A Hershberger; Laura P Stabile; Beatriz Kanterewicz; Mary E Rothstein; Chris T Gubish; Stephanie Land; Yongli Shuai; Jill M Siegfried; Mark Nichols
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-19
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  116     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-10-26     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  102-9     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Non-Small-Cell Lung / enzymology*,  genetics*,  metabolism
Cell Line, Tumor
Estrogen Receptor beta / agonists*,  metabolism
Genistein / pharmacology
Ginsenosides / pharmacology
Lung Neoplasms / enzymology*,  genetics*,  metabolism
Mitogen-Activated Protein Kinase 1 / genetics,  metabolism*
Nitriles / pharmacology
Protein Kinase Inhibitors / pharmacology
Sapogenins / pharmacology
Transcription Factors / genetics,  metabolism*
Transcription, Genetic*
Grant Support
P50 CA090440/CA/NCI NIH HHS; P50 CA090440-090006/CA/NCI NIH HHS; P50 CA90440/CA/NCI NIH HHS
Reg. No./Substance:
0/2,3-bis(4-hydroxyphenyl)-propionitrile; 0/Estrogen Receptor beta; 0/Ginsenosides; 0/Ligands; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Sapogenins; 0/Transcription Factors; 0/ginsenoside 20S-protopanaxatriol; 0/p44 protein, human; DH2M523P0H/Genistein; EC Protein Kinase 1

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