Journal
CANCER INVESTIGATION
Volume 28, Issue 6, Pages 588-597Publisher
INFORMA HEALTHCARE
DOI: 10.3109/07357900903286941
Keywords
p16; VEGF; HIF-1 alpha; Breast cancer
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Funding
- National Institutes of Health [CA107162]
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The degree of tumor progression (such as growth, angiogenesis, and metastasis) directly correlates with the expression of vascular endothelial growth factor (VEGF), but inversely correlates with the expression of tumor-suppressor gene p16, therefore we examined whether the restoration of p16 in breast cancer cells would modulate VEGF expression. Adenoviral-mediated p16 expression downregulated VEGF gene expression in breast cancer cells, and inhibited breast cancer cell-induced angiogenesis by a dorsal air sac model in mice. Moreover, p16 appears to form a complex with HIF-1 alpha, the transcription factor for the VEGF gene promoter. Taken together, the binding between p16 and HIF-1a protein may alter HIF-1 alpha's ability to transactivate VEGF expression.
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