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000013100 0247_ $$2DOI$$a10.1210/me.2010-0125
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000013100 084__ $$2WoS$$aEndocrinology & Metabolism
000013100 1001_ $$0P:(DE-HGF)0$$aZhang, G.$$b0
000013100 245__ $$aLigand-independent antiapoptotic function of estrogen receptor-beta in lung cancer cells
000013100 260__ $$aBethesda, Md.$$bEndocrine Society$$c2010
000013100 300__ $$a1737 - 1747
000013100 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000013100 3367_ $$2DRIVER$$aarticle
000013100 440_0 $$023401$$aMolecular Endocrinology$$v24$$x0888-8809$$y9
000013100 500__ $$aThis work was supported by the Career Development Award from the University of Pittsburgh Specialized Program of Research Excellence (SPORE) in Lung Cancer and by the Core Grant for Vision Research EY08098.
000013100 520__ $$aRecent studies have demonstrated the presence of estrogen receptor (ER)beta in the mitochondria in various cell types and tissues, but the exact function of this localization remains unclear. In this study, we have examined the function of mitochondrial ERbeta in non-small-cell lung cancer (NSCLC) cells. Down-regulation of ERbeta by short hairpin RNA constructs sensitized NSCLC cells to various apoptosis-inducing agents such as cisplatin, taxol, and etoposide. The increased growth inhibition and induction of apoptosis in ERbeta-knockdown cells was observed irrespective of estrogen treatment, suggesting a ligand-independent role of ERbeta in regulating the intrinsic apoptotic pathway. Further, ERbeta from the mitochondrial fraction physically interacted with the proapoptotic protein Bad, in a ligand-independent manner. Glutathione-S-transferase pull-down assays and molecular modeling studies revealed that the DNA-binding domain and hinge region of ERbeta, and the BH3 domain of Bad were involved in these interactions. Further investigations revealed that ERbeta inhibited Bad function by disrupting Bad-Bcl-X(L) and Bad-Bcl-2 interactions. Reintroduction of ERbeta in the mitochondria of ERbeta knockdown cells reversed their sensitivity to cisplatin. Overall, our results demonstrate a ligand-independent role of ERbeta in regulating apoptosis, revealing a novel function for ERbeta in the mitochondria.
000013100 536__ $$0G:(DE-Juel1)FUEK505$$2G:(DE-HGF)$$aBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$cP45$$x0
000013100 588__ $$aDataset connected to Web of Science, Pubmed
000013100 650_2 $$2MeSH$$aApoptosis: drug effects
000013100 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: metabolism
000013100 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: pathology
000013100 650_2 $$2MeSH$$aCell Line, Tumor
000013100 650_2 $$2MeSH$$aCell Survival: drug effects
000013100 650_2 $$2MeSH$$aCisplatin: pharmacology
000013100 650_2 $$2MeSH$$aEstrogen Receptor beta: chemistry
000013100 650_2 $$2MeSH$$aEstrogen Receptor beta: metabolism
000013100 650_2 $$2MeSH$$aGene Knockdown Techniques
000013100 650_2 $$2MeSH$$aHumans
000013100 650_2 $$2MeSH$$aImmunoprecipitation
000013100 650_2 $$2MeSH$$aInhibitory Concentration 50
000013100 650_2 $$2MeSH$$aLigands
000013100 650_2 $$2MeSH$$aLung Neoplasms: metabolism
000013100 650_2 $$2MeSH$$aLung Neoplasms: pathology
000013100 650_2 $$2MeSH$$aMitochondria: drug effects
000013100 650_2 $$2MeSH$$aMitochondria: metabolism
000013100 650_2 $$2MeSH$$aModels, Biological
000013100 650_2 $$2MeSH$$aModels, Molecular
000013100 650_2 $$2MeSH$$aProtein Binding: drug effects
000013100 650_2 $$2MeSH$$aProtein Structure, Tertiary
000013100 650_2 $$2MeSH$$aProtein Transport: drug effects
000013100 650_2 $$2MeSH$$aRNA, Small Interfering: metabolism
000013100 650_2 $$2MeSH$$abcl-Associated Death Protein: chemistry
000013100 650_2 $$2MeSH$$abcl-Associated Death Protein: metabolism
000013100 650_2 $$2MeSH$$abcl-X Protein: metabolism
000013100 650_7 $$00$$2NLM Chemicals$$aEstrogen Receptor beta
000013100 650_7 $$00$$2NLM Chemicals$$aLigands
000013100 650_7 $$00$$2NLM Chemicals$$aRNA, Small Interfering
000013100 650_7 $$00$$2NLM Chemicals$$abcl-Associated Death Protein
000013100 650_7 $$00$$2NLM Chemicals$$abcl-X Protein
000013100 650_7 $$015663-27-1$$2NLM Chemicals$$aCisplatin
000013100 650_7 $$2WoSType$$aJ
000013100 7001_ $$0P:(DE-HGF)0$$aYanamala, N.$$b1
000013100 7001_ $$0P:(DE-HGF)0$$aLathrop, KL.$$b2
000013100 7001_ $$0P:(DE-HGF)0$$aZhang, L.$$b3
000013100 7001_ $$0P:(DE-Juel1)VDB44599$$aKlein-Seetharaman, J.$$b4$$uFZJ
000013100 7001_ $$0P:(DE-HGF)0$$aSrinivas, H.$$b5
000013100 773__ $$0PERI:(DE-600)1492112-1$$a10.1210/me.2010-0125$$gVol. 24, p. 1737 - 1747$$p1737 - 1747$$q24<1737 - 1747$$tMolecular endocrinology$$v24$$x0888-8809$$y2010
000013100 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940472
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000013100 9132_ $$0G:(DE-HGF)POF3-551$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lBioSoft  Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vFunctional Macromolecules and Complexes$$x0
000013100 9201_ $$0I:(DE-Juel1)ISB-2-20090406$$d31.12.2010$$gISB$$kISB-2$$lMolekulare Biophysik$$x0
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