Title
Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells
UMMS Affiliation
Department of Cancer Biology
Publication Date
2004-07-17
Document Type
Article
Subjects
Apoptosis; Breast 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
Disciplines
Cancer Biology | Neoplasms
Abstract
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.
DOI of Published Version
10.1158/0008-5472.CAN-04-0347
Source
Cancer Res. 2004 Jul 15;64(14):4711-6. Link to article on publisher's site
Journal/Book/Conference Title
Cancer research
Related Resources
PubMed ID
15256436
Repository Citation
Chung J, Yoon S, Datta K, Bachelder RE, Mercurio AM. (2004). Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells. Cancer Biology Publications and Presentations. https://doi.org/10.1158/0008-5472.CAN-04-0347. Retrieved from https://escholarship.umassmed.edu/cancerbiology_pp/173