cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: Implication in human prostate cancer bone metastasis

D. Wu, H. E. Zhau, W. C. Huang, S. Iqbal, F. K. Habib, O. Sartor, L. Cvitanovic, F. F. Marshall, Z. Xu, L. W.K. Chung

Research output: Contribution to journalArticle

98 Scopus citations

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 languageEnglish (US)
Pages (from-to)5070-5077
Number of pages8
JournalOncogene
Volume26
Issue number35
DOIs
StatePublished - Aug 2 2007

Keywords

  • Bone metastasis
  • CREB
  • EMT
  • HIF
  • Prostate cancer
  • VEGF

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Wu, D., Zhau, H. E., Huang, W. C., Iqbal, S., Habib, F. K., Sartor, O., Cvitanovic, L., Marshall, F. F., Xu, Z., & Chung, L. W. K. (2007). cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: Implication in human prostate cancer bone metastasis. Oncogene, 26(35), 5070-5077. https://doi.org/10.1038/sj.onc.1210316