Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on α6β1 integrin in breast carcinoma cells

Jun Chung, Sangoh Yoon, Kaustubh Datta, Robin E. Bachelder, Arthur M. Mercurio

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The α6β1 integrin has been implicated in breast carcinoma progression, but the mechanisms involved remain elusive. MDA-MB-435 cells engineered to be deficient in α6β1 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 α6β1 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 α6β1 expression. We investigated the influence of α6β1 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 α6β1 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 α6β1 expression by a mechanism that involves protein kinase C-α.

Original languageEnglish (US)
Pages (from-to)4711-4716
Number of pages6
JournalCancer Research
Volume64
Issue number14
DOIs
StatePublished - Jul 15 2004

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Integrins
Vascular Endothelial Growth Factor A
Apoptosis
Breast Neoplasms
Cell Hypoxia
Tumor Microenvironment
Serum
Protein Kinase C
Cell Survival
Hypoxia
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on α6β1 integrin in breast carcinoma cells. / Chung, Jun; Yoon, Sangoh; Datta, Kaustubh; Bachelder, Robin E.; Mercurio, Arthur M.

In: Cancer Research, Vol. 64, No. 14, 15.07.2004, p. 4711-4716.

Research output: Contribution to journalArticle

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