Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells

Qian Shi; Xiangdong Le; Bailiang Wang; James L. Abbruzzese; Qinghua Xiong; Yanjuan He; Keping Xie

doi:10.1038/sj.onc.1204500

Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells

Qian Shi, Xiangdong Le, Bailiang Wang, James L. Abbruzzese, Qinghua Xiong, Yanjuan He, Keping Xie

Gastroenterology Hepatology & Nutrition

Research output: Contribution to journal › Article › peer-review

218 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3751-3756
Number of pages	6
Journal	Oncogene
Volume	20
Issue number	28
DOIs	https://doi.org/10.1038/sj.onc.1204500
State	Published - Jun 21 2001

Keywords

Acidosis
Angiogenesis
Pancreatic cancer
Regulation
VEGF

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1204500

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title = "Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells",

abstract = "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.",

keywords = "Acidosis, Angiogenesis, Pancreatic cancer, Regulation, VEGF",

author = "Qian Shi and Xiangdong Le and Bailiang Wang and Abbruzzese, {James L.} and Qinghua Xiong and Yanjuan He and Keping Xie",

note = "Funding Information: We thank Don Norwood for editorial comments and Judy King for assistance in the preparation of this manuscript. This work was supported in part by the Multidisciplinary Pancreatic Program Research Grant, by Research Project Grant #RPG-00-054-01-CMS from the American Cancer Society, and by Cancer Center Support Core Grant CA16672-23 from the National Cancer Institute (to K Xie).",

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doi = "10.1038/sj.onc.1204500",

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AU - Shi, Qian

AU - Le, Xiangdong

AU - Wang, Bailiang

AU - Abbruzzese, James L.

AU - Xiong, Qinghua

AU - He, Yanjuan

AU - Xie, Keping

N1 - Funding Information: We thank Don Norwood for editorial comments and Judy King for assistance in the preparation of this manuscript. This work was supported in part by the Multidisciplinary Pancreatic Program Research Grant, by Research Project Grant #RPG-00-054-01-CMS from the American Cancer Society, and by Cancer Center Support Core Grant CA16672-23 from the National Cancer Institute (to K Xie).

PY - 2001/6/21

Y1 - 2001/6/21

N2 - 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.

AB - 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.

KW - Acidosis

KW - Angiogenesis

KW - Pancreatic cancer

KW - Regulation

KW - VEGF

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Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells

Abstract

Keywords

ASJC Scopus subject areas

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