Abstract
Aberrant expression of vascular endothelial growth factor (VEGF) is associated with human prostate cancer (PCa) metastasis and poor clinical outcome. We found that both phosphorylation of cyclic AMP-responsive element-binding protein (CREB) and VEGF levels were significantly elevated in patient bone metastatic PCa specimens. A PCa ARCaP progression model demonstrating epithelial-to-mesenchymal transition exhibited increased CREB phosphorylation and VEGF expression as ARCaP cells became progressively more mesenchymal and bone-metastatic. Activation of CREB induced, whereas inhibition of CREB blocked, VEGF expression in ARCaP cells. CREB may regulate VEGF transcription via a hypoxia-inducible factor-dependent mechanism in normoxic conditions. Activation of CREB signaling is involved in the coordinated regulation of VEGF and may pre-dispose to PCa bone metastasis.
Original language | English (US) |
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Pages (from-to) | 5070-5077 |
Number of pages | 8 |
Journal | Oncogene |
Volume | 26 |
Issue number | 35 |
DOIs | |
State | Published - Aug 2 2007 |
Externally published | Yes |
Keywords
- Bone metastasis
- CREB
- EMT
- HIF
- Prostate cancer
- VEGF
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research