Abstract
In brain, breast, and other common human tumors there is a correlation between expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and tumor grade and vascularization. HIF-1 stimulates angiogenesis by activating transcription of the gene encoding vascular endothelial growth factor (VEGF). HIF-1 is a heterodimer consisting of a constitutively-expressed HIF-1β subunit and an O2- and growth factor-regulated HIF-1α subunit. Recent studies have demonstrated that HIF-1α expression is increased in tumor relative to normal tissue by two mechanisms. First, decreased intratumoral O2 concentrations provide a physiological stimulus. Second, genetic alterations that activate oncogene products or inactivate tumor suppressor gene products increase HIF-1α expression and/or HIF-1 transcriptional activity independent of the O2 concentration. Taken together, these recent data suggest that increased HIF-1 activity provides a molecular basis for VEGF-induced angiogenesis and other adaptations of cancer cells to hypoxia that are critical for establishment of a primary tumor and its progression to the lethal phenotype.
Original language | English (US) |
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Pages (from-to) | 59-65 |
Number of pages | 7 |
Journal | Cancer and Metastasis Reviews |
Volume | 19 |
Issue number | 1-2 |
DOIs | |
State | Published - 2000 |
Keywords
- AKT
- MAP kinase
- P53
- PTEN
- Phosphatidylinositol-3-kinase
- SRC
- Vascular endothelial growth factor
- Von Hippel-Lindau protein
ASJC Scopus subject areas
- Oncology
- Cancer Research