Multiple regulatory pathways of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in tumors.
VPF/VEGF is a multi-functional cytokine with important roles in both vasculogenesis and angiogenesis. Its production is generally regulated by local oxygen concentration. Hypoxia stimulates VPF/VEGF production by increasing its gene transcription and the stability of its mRNA. The increase in transcription in hypoxia occurs mainly through the stabilization and activation of the transcription factor, Hypoxia Inducible Factor (HIF). Cellular oxygen concentration is not the only regulator of VPF/VEGF synthesis. Some cancer cells can produce high levels of VPF/VEGF even in normoxia. Clear cell renal carcinoma cell line (RCC) like 786-0, pancreatic carcinoma cell line, ASPC-1, fibrocarcinoma cell line, HT1080, ovarian cancer cells, etc. produce an elevated level of VPF/VEGF, which is not dependent on hypoxia. In this article, we discuss different regulatory pathways in tumor cells comprised of oncogenes, tumor suppressor genes etc. that play important roles, in both the transcription and stability of VPF/VEGF mRNA.
Mukhopadhyay
Debabrata
D
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. dmukhopa@bidmc.harvard.edu
Datta
Kaustubh
K
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019061:src-Family Kinases / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D011493:Protein Kinase C; D011506:Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019061:src-Family Kinases; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C497446:VHL protein, human