Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells

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dc.contributor.authorChung, Jun
dc.contributor.authorYoon, Sangoh
dc.contributor.authorDatta, Kaustubh
dc.contributor.authorBachelder, Robin E.
dc.contributor.authorMercurio, Arthur M.
dc.contributor.departmentDepartment of Cancer Biology
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:49Z
dc.date.available2022-08-23T15:39:49Z
dc.date.issued2004-07-17
dc.date.submitted2010-11-07
dc.description.abstractThe alpha6beta1 integrin has been implicated in breast carcinoma progression, but the mechanisms involved remain elusive. MDA-MB-435 cells engineered to be deficient in alpha6beta1 expression form primary tumors that are highly apoptotic and unable to metastasize, although they exhibit no increased apoptosis in vitro under standard culture conditions. Based on the hypothesis that alpha6beta1 is necessary for the survival of these cells in the tumor microenvironment, we report here that hypoxia protects these cells from apoptosis induced by serum deprivation and that hypoxia-mediated protection requires alpha6beta1 expression. We investigated the influence of alpha6beta1 on vascular endothelial growth factor (VEGF) expression because autocrine VEGF is necessary for the survival of serum-deprived cells in hypoxia. The results obtained indicate that alpha6beta1 is necessary for VEGF expression because the ability of hypoxia to activate HIF-1 and to stimulate VEGF transcription in MDA-MB-435 cells is dependent on alpha6beta1 expression by a mechanism that involves protein kinase C-alpha.
dc.identifier.citationCancer Res. 2004 Jul 15;64(14):4711-6. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-04-0347">Link to article on publisher's site</a>
dc.identifier.contextkey1633398
dc.identifier.doi10.1158/0008-5472.CAN-04-0347
dc.identifier.issn0008-5472 (Linking)
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/173
dc.identifier.pmid15256436
dc.identifier.submissionpathcancerbiology_pp/173
dc.identifier.urihttps://hdl.handle.net/20.500.14038/26259
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15256436&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/0008-5472.CAN-04-0347
dc.source.issue14
dc.source.journaltitleCancer research
dc.source.pages4711-6
dc.source.volume64
dc.subjectApoptosis
dc.subjectBreast Neoplasms
dc.subjectCell Hypoxia
dc.subjectCell Line, Tumor
dc.subjectDNA-Binding Proteins
dc.subjectHumans
dc.subjectHypoxia-Inducible Factor 1
dc.subjectHypoxia-Inducible Factor 1, alpha Subunit
dc.subjectIntegrin alpha6beta1
dc.subjectNuclear Proteins
dc.subjectProtein Kinase C
dc.subjectProtein Kinase C-alpha
dc.subject*Transcription Factors
dc.subjectTranscription, Genetic
dc.subjectTranscriptional Activation
dc.subjectVascular Endothelial Growth Factor A
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleHypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells
dc.typeJournal Article
dspace.entity.typePublication
html.description.abstract<p>The alpha6beta1 integrin has been implicated in breast carcinoma progression, but the mechanisms involved remain elusive. MDA-MB-435 cells engineered to be deficient in alpha6beta1 expression form primary tumors that are highly apoptotic and unable to metastasize, although they exhibit no increased apoptosis in vitro under standard culture conditions. Based on the hypothesis that alpha6beta1 is necessary for the survival of these cells in the tumor microenvironment, we report here that hypoxia protects these cells from apoptosis induced by serum deprivation and that hypoxia-mediated protection requires alpha6beta1 expression. We investigated the influence of alpha6beta1 on vascular endothelial growth factor (VEGF) expression because autocrine VEGF is necessary for the survival of serum-deprived cells in hypoxia. The results obtained indicate that alpha6beta1 is necessary for VEGF expression because the ability of hypoxia to activate HIF-1 and to stimulate VEGF transcription in MDA-MB-435 cells is dependent on alpha6beta1 expression by a mechanism that involves protein kinase C-alpha.</p>
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