Vasoactive intestinal peptide increases vascular endothelial growth factor expression and neuroendocrine differentiation in human prostate cancer LNCaP cells.
Vasoactive intestinal peptide (VIP) upregulates the expression of vascular endothelial cell growth factor (VEGF(189), VEGF(165) and VEGF(121)) mRNAs in human prostate cancer LNCaP cells, as shown by reverse transcriptase-polymerase chain reaction (RT-PCR). Real-time RT-PCR indicated that the effect was maximal by 1-2 h and must be accounted for increased transcription since VIP decreased VEGF(165) mRNA stability. VIP stimulated VEGF(165) protein synthesis as measured by ELISA. VIP regulation of VEGF expression was mediated by VPAC(1) receptor and was cAMP/protein kinase A (PKA) dependent. Phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase MEK1/2 systems may also be involved as shown with specific kinase inhibitors. These actions together with the observation of VIP-induced neuroendocrine differentiation in LNCaP cells suggest a proangiogenic potential of VIP in prostate cancer.
Collado
Beatriz
B
Molecular Neuroendocrinology Unit, Department of Biochemistry and Molecular Biology, Alcalá University, E-28871 Alcalá de Henares, Spain.
Gutiérrez-Cañas
Irene
I
Rodríguez-Henche
Nieves
N
Prieto
Juan C
JC
Carmena
María J
MJ
D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D009490:Neurosecretory Systems / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014660:Vasoactive Intestinal Peptide; D012313:RNA; D000242:Cyclic AMP; C482128:MAP2K2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human