Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2004-07-17Keywords
ApoptosisBreast Neoplasms
Cell Hypoxia
Cell Line, Tumor
DNA-Binding Proteins
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Integrin alpha6beta1
Nuclear Proteins
Protein Kinase C
Protein Kinase C-alpha
*Transcription Factors
Transcription, Genetic
Transcriptional Activation
Vascular Endothelial Growth Factor A
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
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.Source
Cancer Res. 2004 Jul 15;64(14):4711-6. Link to article on publisher's siteDOI
10.1158/0008-5472.CAN-04-0347Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26259PubMed ID
15256436Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-04-0347
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