Increased VEGF165 expression in HCT116 colon cancer cells after transient transfection with a GFP vector encoding HIF-1 gene.
Hypoxia occurs in most solid tumors as a result of inefficient vascular development and/or abnormal vascular architecture. During hypoxia, HIF-1alpha acts as the primary transcription factor functioning to activate multiple target genes, including vascular endothelial growth factor (VEGF). Several studies have demonstrated that in tumors HIF-1alpha mediates VEGF protein expression at the transcription level. We aimed to establish whether HCT116 colon cancer cell VEGF expression is regulated by HIF-1 levels after transient transfection with a GFP vector encoding the HIF-1alpha gene. HCT116 cell VEGF expression were therefore assayed by immunohistochemistry and ELISA. After transfection with phMGFP-HIF-1alpha, VEGF immunostaining was significantly increased in transfected cells as compared with untransfected HCT116 cells (p = 0.024, Student's t test); culture media VEGF levels assayed by ELISA were also significantly increased in transfected cells (p = 0.008, Student's t-test). These data suggest that HIF-1alpha may play an important role in colon cancer angiogenesis, both as a biomarker of metastatic potential and as a novel target for gene therapy.
Lucarini
G
G
Department of Molecular Pathology and Innovative Therapies, Histology, Polytechnic University of Marche Region, Italy. guendalina.lucarini@univpm.it
Zizzi
A
A
Belvederesi
L
L
Kyriakidou
K
K
Mazzucchelli
R
R
Biagini
G
G
D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins