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dc.contributor.authorLipscomb, Elizabeth A.
dc.contributor.authorSimpson, Kaylene J.
dc.contributor.authorLyle, Stephen
dc.contributor.authorRing, Jennifer E.
dc.contributor.authorDugan, Aisling S.
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:52Z
dc.date.available2022-08-23T15:39:52Z
dc.date.issued2005-12-03
dc.date.submitted2010-11-07
dc.identifier.citationCancer Res. 2005 Dec 1;65(23):10970-6. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-05-2327">Link to article on publisher's site</a>
dc.identifier.issn0008-5472 (Linking)
dc.identifier.doi10.1158/0008-5472.CAN-05-2327
dc.identifier.pmid16322245
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26271
dc.description.abstractThe alpha6beta4 integrin has been widely implicated in carcinoma function in vitro; however, in vivo data are scarce. To determine the importance of alpha6beta4 in tumor progression, a SUM-159 breast carcinoma cell line that is essentially devoid of alpha6beta4 expression was generated using an RNA interference strategy. Loss of alpha6beta4 expression inhibits colony formation in soft agar assays, suggesting a vital role for alpha6beta4 in survival signaling and anchorage-independent growth. Orthotopic injection of the beta4-deficient cell line into the mammary fat pad of immunocompromised mice yielded significantly fewer and smaller tumors than the control cell line, revealing a role for the alpha6beta4 integrin in tumor formation. Under conditions that mimicked the in vivo environment, decreased expression of the alpha6beta4 integrin led to enhanced apoptosis as determined by the percentage of Annexin V-FITC+, PI- cells and the presence of caspase-3 cleavage products. Recombinant vascular endothelial growth factor (VEGF) significantly inhibited the cell death observed in the beta4-deficient cell line, demonstrating the importance of VEGF expression in this survival pathway. Furthermore, loss of alpha6beta4 expression leads to enhanced apoptosis and reduced expression of VEGF in breast carcinoma cells in vivo. Importantly, the specificity of alpha6beta4 in both the in vitro and in vivo assays showed that reexpression of the beta4 subunit into the beta4-deficient cell line could rescue the functional phenotype. Taken together, these data implicate the alpha6beta4 integrin in tumor formation by regulating tumor cell survival in a VEGF-dependent manner.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16322245&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/0008-5472.CAN-05-2327
dc.subjectApoptosis
dc.subjectBreast Neoplasms
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectHumans
dc.subjectIntegrin alpha6beta4
dc.subjectIntegrin beta4
dc.subjectNeoplastic Stem Cells
dc.subjectRNA, Messenger
dc.subjectRNA, Small Interfering
dc.subjectVascular Endothelial Growth Factor A
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleThe alpha6beta4 integrin maintains the survival of human breast carcinoma cells in vivo
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume65
dc.source.issue23
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/185
dc.identifier.contextkey1633411
html.description.abstract<p>The alpha6beta4 integrin has been widely implicated in carcinoma function in vitro; however, in vivo data are scarce. To determine the importance of alpha6beta4 in tumor progression, a SUM-159 breast carcinoma cell line that is essentially devoid of alpha6beta4 expression was generated using an RNA interference strategy. Loss of alpha6beta4 expression inhibits colony formation in soft agar assays, suggesting a vital role for alpha6beta4 in survival signaling and anchorage-independent growth. Orthotopic injection of the beta4-deficient cell line into the mammary fat pad of immunocompromised mice yielded significantly fewer and smaller tumors than the control cell line, revealing a role for the alpha6beta4 integrin in tumor formation. Under conditions that mimicked the in vivo environment, decreased expression of the alpha6beta4 integrin led to enhanced apoptosis as determined by the percentage of Annexin V-FITC+, PI- cells and the presence of caspase-3 cleavage products. Recombinant vascular endothelial growth factor (VEGF) significantly inhibited the cell death observed in the beta4-deficient cell line, demonstrating the importance of VEGF expression in this survival pathway. Furthermore, loss of alpha6beta4 expression leads to enhanced apoptosis and reduced expression of VEGF in breast carcinoma cells in vivo. Importantly, the specificity of alpha6beta4 in both the in vitro and in vivo assays showed that reexpression of the beta4 subunit into the beta4-deficient cell line could rescue the functional phenotype. Taken together, these data implicate the alpha6beta4 integrin in tumor formation by regulating tumor cell survival in a VEGF-dependent manner.</p>
dc.identifier.submissionpathcancerbiology_pp/185
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages10970-6


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