title: cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: implication in human prostate cancer bone metastasis.
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.
authors.affiliation: Molecular Urology and Therapeutics Program, Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA. dwu2@emory.edu
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: H E
authors.initials: HE
authors.lastname: Zhau
authors.forename: W-C
authors.initials: WC
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: F K
authors.initials: FK
authors.lastname: Habib
authors.forename: O
authors.initials: O
authors.lastname: Sartor
authors.forename: L
authors.initials: L
authors.lastname: Cvitanovic
authors.forename: F F
authors.initials: FF
authors.lastname: Marshall
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: L W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A