001     13100
005     20200402205938.0
024 7 _ |2 pmid
|a pmid:20660297
024 7 _ |2 pmc
|a pmc:PMC2940472
024 7 _ |2 DOI
|a 10.1210/me.2010-0125
024 7 _ |2 WOS
|a WOS:000281387300005
037 _ _ |a PreJuSER-13100
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Endocrinology & Metabolism
100 1 _ |0 P:(DE-HGF)0
|a Zhang, G.
|b 0
245 _ _ |a Ligand-independent antiapoptotic function of estrogen receptor-beta in lung cancer cells
260 _ _ |a Bethesda, Md.
|b Endocrine Society
|c 2010
300 _ _ |a 1737 - 1747
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 23401
|a Molecular Endocrinology
|v 24
|x 0888-8809
|y 9
500 _ _ |a This 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.
520 _ _ |a Recent 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.
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|2 G:(DE-HGF)
|a BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung
|c P45
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Apoptosis: drug effects
650 _ 2 |2 MeSH
|a Carcinoma, Non-Small-Cell Lung: metabolism
650 _ 2 |2 MeSH
|a Carcinoma, Non-Small-Cell Lung: pathology
650 _ 2 |2 MeSH
|a Cell Line, Tumor
650 _ 2 |2 MeSH
|a Cell Survival: drug effects
650 _ 2 |2 MeSH
|a Cisplatin: pharmacology
650 _ 2 |2 MeSH
|a Estrogen Receptor beta: chemistry
650 _ 2 |2 MeSH
|a Estrogen Receptor beta: metabolism
650 _ 2 |2 MeSH
|a Gene Knockdown Techniques
650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Immunoprecipitation
650 _ 2 |2 MeSH
|a Inhibitory Concentration 50
650 _ 2 |2 MeSH
|a Ligands
650 _ 2 |2 MeSH
|a Lung Neoplasms: metabolism
650 _ 2 |2 MeSH
|a Lung Neoplasms: pathology
650 _ 2 |2 MeSH
|a Mitochondria: drug effects
650 _ 2 |2 MeSH
|a Mitochondria: metabolism
650 _ 2 |2 MeSH
|a Models, Biological
650 _ 2 |2 MeSH
|a Models, Molecular
650 _ 2 |2 MeSH
|a Protein Binding: drug effects
650 _ 2 |2 MeSH
|a Protein Structure, Tertiary
650 _ 2 |2 MeSH
|a Protein Transport: drug effects
650 _ 2 |2 MeSH
|a RNA, Small Interfering: metabolism
650 _ 2 |2 MeSH
|a bcl-Associated Death Protein: chemistry
650 _ 2 |2 MeSH
|a bcl-Associated Death Protein: metabolism
650 _ 2 |2 MeSH
|a bcl-X Protein: metabolism
650 _ 7 |0 0
|2 NLM Chemicals
|a Estrogen Receptor beta
650 _ 7 |0 0
|2 NLM Chemicals
|a Ligands
650 _ 7 |0 0
|2 NLM Chemicals
|a RNA, Small Interfering
650 _ 7 |0 0
|2 NLM Chemicals
|a bcl-Associated Death Protein
650 _ 7 |0 0
|2 NLM Chemicals
|a bcl-X Protein
650 _ 7 |0 15663-27-1
|2 NLM Chemicals
|a Cisplatin
650 _ 7 |2 WoSType
|a J
700 1 _ |0 P:(DE-HGF)0
|a Yanamala, N.
|b 1
700 1 _ |0 P:(DE-HGF)0
|a Lathrop, KL.
|b 2
700 1 _ |0 P:(DE-HGF)0
|a Zhang, L.
|b 3
700 1 _ |0 P:(DE-Juel1)VDB44599
|a Klein-Seetharaman, J.
|b 4
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Srinivas, H.
|b 5
773 _ _ |0 PERI:(DE-600)1492112-1
|a 10.1210/me.2010-0125
|g Vol. 24, p. 1737 - 1747
|p 1737 - 1747
|q 24<1737 - 1747
|t Molecular endocrinology
|v 24
|x 0888-8809
|y 2010
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940472
909 C O |o oai:juser.fz-juelich.de:13100
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914 1 _ |y 2010
915 _ _ |0 StatID:(DE-HGF)0010
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