Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells.
The influence of acidosis on the expression of the vascular endothelial growth factor (VEGF) gene was determined. FG human pancreatic adenocarcinoma cells were incubated for various time periods in media at a physiologically relevant pH level (6.7-7.4). The expression of VEGF mRNA and protein secretion was inversely correlated with pH in a pH- and time-dependent manner. Transient acidosis also activated the VEGF promoter/enhancer luciferase reporter, which was consistent with an increased VEGF gene transcription rate and VEGF mRNA half-life. These data indicated that acidosis transcriptionally and posttranscriptionally regulates VEGF expression, suggesting that an acidic tumor microenvironment contributes to tumor angiogenesis and progression.
Shi
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Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, TX 77030, USA.
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Wang
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Abbruzzese
J L
JL
Xiong
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He
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Xie
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D020413:3' Untranslated Regions; D000143:Acids; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016209:Interleukin-8 / Q000235:genetics; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D008297:Male; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020413:3' Untranslated Regions; D000143:Acids; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2