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.
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References
Akiri G, Nahari D, Finkelstein Y, Le S, Elroy-Stein O, Levi B . 1998 Oncogene 12: 227–236
Bellocq A, Suberville S, Philippe C, Bertrand F, Perez J, Fouqueray B, Cherqui G, Baud L . 1998 J. Biol. Chem. 273: 5086–5092
Blancher C, Harris AL . 1998 Cancer Metastasis Rev. 17: 187–194
Boucher Y, Baxter LT, Jain RK . 1990 Cancer Res. 50: 4478–4484
Brooks SE, Gu X, Kaufmann PM, Marcus DM, Caldwell RB . 1998 Curr. Eye Res. 17: 875–882
Claffey KP, Shih SC, Mullen A, Dziennis S, Cusick JL, Abrams KR, Lee SW, Detmar M . 1998 Mol. Biol. Cell 9: 469–481
Damert A, Machein M, Breier G, Fujita MQ, Hanahan D, Risau W, Plate KH . 1997 Cancer Res. 57: 3860–3864
D'Arcangelo D, Facchiano F, Barlucchi LM, Melillo G, Illi B, Testolin L, Gaetano C, Capogrossi MC . 2000 Circ. Res. 86: 312–318
Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y . 1997 Proc. Natl. Acad. Sci. USA 94: 4273–4278
Finkenzeller G, Technau A, Marme D . 1995 Biochem. Biophys. Res. Commun. 208: 432–439
Flamme I, Frohlich T, Vonreutern M, Kappel A, Damert A, Risau W . 1997 Mech. Dev. 63: 51–60
Folkman J . 1996 Nat. Med. 2: 167–168
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL . 1996 Mol. Cell Biol. 16: 4604–4613
Griffiths L, Dachs GU, Bicknell R, Harris AL, Stratford IJ . 1997 Cancer Res. 57: 570–572
Huang S, Jean D, Luca M, Tainsky MA, Bar-Eli M . 1998 EMBO J. 17: 4358–4369
Huang S, Robinson JB, DeGuzman A, Bucana CD, Fidler IJ . 2000 Cancer Res. 60: 5334–5339
Intaglietta M . 1977 Med. Instrum. 11: 149–152
Itakura J, Ishiwata T, Friess H, Fujii H, Matsumoto Y, Buchler MW, Korc M . 1997 Clin. Cancer Res. 3: 1309–1316
Jang A, Hill RP . 1997 Clin. Exp. Metastasis 15: 469–483
Kallinowski F, Vaupel P . 1988 Br. J. Cancer 58: 314–321
Ladoux A, Frelin C . 1994 Biochem. Biophys. Res. Commun. 204: 794–798
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N . 1989 Science 246: 1306–1309
Levy AP, Levy NS, Goldberg MA . 1996 J. Biol. Chem. 271: 25492–25497
Liu YX, Cox SR, Morita T, Kourembanas S . 1995 Circ. Res. 77: 638–643
Rotin D, Steele-Norwood D, Grinstein S, Tannock I . 1989 Cancer Res. 49: 205–211
Scott PA, Gleadie JM, Bicknell R, Harris AL . 1998 Int. J. Cancer 75: 706–712
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF . 1983 Science 219: 983–985
Shi Q, Abbruzzese JL, Huang S, Fidler IJ, Xiong Q, Xie K . 1999 Clin. Cancer Res. 5: 7234–7243
Shi Q, Le X, Wang B, Xiong Q, Abbruzzese JL, Xie K . 2000 J. Interferon Cytokine Res. 20: 1544–1548
Shubik P . 1982 J. Cancer Res. Clin. Oncol. 103: 211–226
Shweiki D, Itin A, Soffer D, Keshet E . 1992 Nature (London) 359: 843–845
Stein I, Neeman M, Shweiki D, Itin A, Keshet E . 1995 Mol. Cell. Biol. 15: 5363–5368
Tannock IF . 1996 J. Clin. Oncol. 14: 3156–3174
Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA . 1991 J. Biol. Chem. 266: 11947–11954
Vezeridis MP, Doremus CM, Tibbetts LM, Tzanakakis G, Jackson BT . 1989 J. Surg. Oncol. 40: 261–265
Vaupel P, Kallinowski F, Okunieff P . 1989 Cancer Res. 49: 6449–6465
Wike-Hooley JL, Haveman J, Reinhold HS . 1984 Radiother. Oncol. 2: 343–366
Watanabe Y, Miura I, Ohgami Y, Fujiwara M . 1998 Life Sci. 63: 1037–1046
Xie K . 2001 Cytokine and Growth Factor Rev. in press
Acknowledgements
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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Shi, Q., Le, X., Wang, B. et al. Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene 20, 3751–3756 (2001). https://doi.org/10.1038/sj.onc.1204500
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DOI: https://doi.org/10.1038/sj.onc.1204500
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