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

被引：208

作者：

Shi, Q

Le, XD

Wang, BL

Abbruzzese, JL

Xiong, QH

He, YJ

Xie, KP

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA

[2] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

来源：

ONCOGENE | 2001年 / 20卷 / 28期

关键词：

angiogenesis; VEGF; regulation; acidosis; pancreatic cancer;

D O I：

10.1038/sj.onc.1204500

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

收藏

页码：3751 / 3756

页数：6

相关论文

共 40 条

[1] Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription [J].

Akiri, G ;

Nahari, D ;

Finkelstein, Y ;

Le, SY ;

Elroy-Stein, O ;

Levi, BZ .

ONCOGENE, 1998, 17 (02) :227-236

[2] Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages -: Evidence for involvement of nuclear factor-κB activation [J].

Bellocq, A ;

Suberville, S ;

Philippe, C ;

Bertrand, F ;

Perez, J ;

Fouqueray, B ;

Cherqui, G ;

Baud, L .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (09) :5086-5092

[3] The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target [J].

Blancher, C ;

Harris, AL .

CANCER AND METASTASIS REVIEWS, 1998, 17 (02) :187-194

[4]

BOUCHER Y, 1990, CANCER RES, V50, P4478

[5] Modulation of VEGF production by pH and glucose in retinal Muller cells [J].

Brooks, SE ;

Gu, XL ;

Kaufmann, PM ;

Marcus, DM ;

Caldwell, RB .

CURRENT EYE RESEARCH, 1998, 17 (09) :875-882

[6] Identification of a human VPF/VEGF 3′ untranslated region mediating hypoxia-induced mRNA stability [J].

Claffey, KP ;

Shih, SC ;

Mullen, A ;

Dziennis, S ;

Cusick, JL ;

Abrams, KR ;

Lee, SW ;

Detmar, M .

MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (02) :469-481

[7] Acidosis inhibits endothelial cell apoptosis and function and induces basic fibroblast growth factor and vascular endothelial growth factor expression [J].

D'Arcangelo, D ;

Facchiano, F ;

Barlucchi, LM ;

Melillo, G ;

Illi, B ;

Testolin, L ;

Gaetano, C ;

Capogrossi, MC .

CIRCULATION RESEARCH, 2000, 86 (03) :312-318

[8]

Damert A, 1997, CANCER RES, V57, P3860

[9] A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1 alpha regulates the VEGF expression and is potentially involved in lung and vascular development [J].

Ema, M ;

Taya, S ;

Yokotani, N ;

Sogawa, K ;

Matsuda, Y ;

FujiiKuriyama, Y .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4273-4278

[10] HYPOXIA-INDUCED TRANSCRIPTION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE IS INDEPENDENT OF FUNCTIONAL AP-1 TRANSCRIPTION FACTOR [J].

FINKENZELLER, G ;

TECHNAU, A ;

MARME, D .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 208 (01) :432-439

← 1 2 3 4 →