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-tomesenchymal 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.

Epidermal Growth Factor Promotes Protein Degradation of Epithelial Protein Lost in Neoplasm (EPLIN), a Putative Metastasis Suppressor, during Epithelial-mesenchymal Transition

“…Nuclear proteins were extracted using a Novagen kit (EMD Biosciences, San Diego, CA). Immunoblotting analysis followed standard procedure (22). Information for the antibodies used in this study is described in Table 1.…”

“…Cells The specific primer pairs are described in Table 3. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was amplified with a pair of primers described previously (22) and used to normalize RNA inputs.…”

Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway

“…Phospho-activated CREB (p-CREB) induces target gene expression and regulates various neuronal functions [15] . A recent study also demonstrated that CREB is crucial for promoting prostate cancer bone metastasis by inducing VEGF expression through HIF-1-dependent signaling [16] , implicating a (high) glucose-[Ca 2+ ] i -CaMKII-CREB-VEGF signaling cascade in DR-associated angiogenesis.…”

Quantum dots-based multiplexed immunohistochemistry of protein expression in human prostate cancer cells

“…The membranes were rinsed with TBS several times and the blots were ready for re-blot with anti-EF-1α antibody (1:1000 dilution). Immunoreactive bands were visualized with enhanced chemiluminescence (Amersham Pharmacia Biotech, Little Chalfont, United Kingdom) using previously established protocols Nomura et al, 2006;Wu et al, 2007).…”