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Expression of the vascular endothelial growth factor gene is inhibited by p73

Oncogene volume 19, pages 3470–3476 (2000)Cite this article

Abstract

Recently, p73, a new member of the p53 family, has been cloned and mapped to chromosome 1p36, a region that is frequently deleted in a variety of human cancers. p73 can activate p53-responsive promoters and induce apoptosis when overexpressed in certain p53-deficient tumor cells. In contrast to p53, analysis of the p73 gene in several human solid tumors did not reveal loss of p73 expression or mutations in the p73 gene. However, transcriptional silencing of the p73 gene by hypermethylation of a CpG island was observed in several leukemias and lymphomas. These lymphoid neoplasms also show increased expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of angiogenesis. To evaluate a possible relationship between p73 status and VEGF expression, we have studied the effect of ectopically expressed p73 on the regulation of the VEGF gene. Our results demonstrate that p73 can down-regulate endogenous VEGF gene expression on mRNA and protein level. This effect is mediated by transcriptional repression of the VEGF promoter and involves the promoter region −85 to −50 bp, containing a cluster of Sp 1 binding sites. Our results suggest a regulatory role for p73 in tumor angiogenesis.

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References

  • Agami R, Blandino G, Oren M and Shaul Y. . 1999 Nature 399: 809–813.

  • Aguayo A, Estey E, Kantarjian H, Mansouri T, Gidel C, Keating M, Giles F, Estrov Z, Barlogie B and Albitar M. . 1999 Blood 94: 3717–3721.

  • Bellamy WT, Richter L, Frutiger Y and Grogan TM. . 1999 Cancer Res. 59: 728–733.

  • Chen CA and Okayama H. . 1988 Bio. Techniques 6: 632–638.

  • Cohen T, Nahari D, Cerem LW, Neufeld G and Levi BZ. . 1996 J. Biol. Chem. 271: 736–741.

  • Corn PG, Kuerbitz SJ, van Noessel MM, Esteller M, Compitello N, Baylin SB and Herman JG. . 1999 Cancer Res. 59: 3352–3356.

  • Dameron KM, Volpert OV, Tainsky MA and Bouck N. . 1994 Science 265: 1582–1584.

  • Diller L, Kassel J, Nelson CE, Gryka MA, Litwak G, Gebhardt M, Bressac B, Ozturk M, Baker SJ, Vogelstein B et al. 1990 Mol. Cell. Biol. 10: 5772–5781.

  • Finkenzeller G, Marmé D, Weich HA and Hug H. . 1992 Cancer Res. 52: 4821–4823.

  • Finkenzeller G, Technau A and Marmé D. . 1995 Biochem. Biophys. Res. Commun. 208: 432–439.

  • Finkenzeller G, Sparacio A, Technau A, Marmé D and Siemeister G. . 1997 Oncogene 15: 669–676.

  • Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh D and Werner S. . 1995 J. Biol. Chem. 270: 12607–12613.

  • Gerber HP, McMurtey A, Kowalski J, Yan M, Keyt BA, Dixit V and Ferrara N. . 1998a J. Biol. Chem. 273: 30366–30343.

  • Gerber HP, Dixit V and Ferrara N. . 1998b J. Biol. Chem. 273: 13313–13316.

  • Gille J, Swerlick R and Caughman SW. . 1997 EMBO J. 16: 750–759.

  • Hanahan D and Folkman J. . 1996 Cell 86: 353–364.

  • Hollstein M, Sidransky D, Vogelstein B and Harris C. . 1991 Science 253: 49–53.

  • Hussong JW, Rodgers GM and Shami PJ. . 2000 Bloodm 95: 309–313.

  • Jost CA, Marin MC and Kaelin Jr WG. . 1997 Nature 389: 191–194.

  • Kaghad M, Bonnet H, Yang A, Creancier L, Blacan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F and Caput D. . 1997 Cell 90: 809–819.

  • Katoh O, Tauchi H, Kawaishi K, Kimura A and Satow Y. . 1995 Cancer Res. 55: 5687–5692.

  • Katoh O, Takahashi T, Oguri T, Kuramoto K, Mihara K, Kobayashi M, Hirata S and Watanabe H. . 1998 Cancer Res. 58: 5565–5569.

  • Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H, Sakashita A, Said J, Tatsumi E and Koeffler HP. . 1999 Blood 94: 1113–1120.

  • Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW and Vogelstein B. . 1992 Science 256: 827–830.

  • Kolch W, Martiny-Baron G, Kieser A and Marmé D. . 1995 Breast Cancer Res. and Treatment 36: 139–155.

  • Kroiss MM, Bosserhoff AK, Vogt T, Buettner R, Bogenrieder T, Landthaler M and Stolz W. . 1998 Melanoma Res. 8: 504–509.

  • Levine AJ, Momand J and Finlay CA. . 1991 Nature 351: 453–456.

  • Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith D and Liu W. . 1998 Cancer Res. 58: 2347–2349.

  • Marin MC, Jost CA, Irwin MS, DeCaprio JA, Caput D and Kaelin Jr WG. . 1998 Mol. Cell. Biol. 18: 6316–6324.

  • Martiny-Baron G and Marmé D. . 1995 Curr. Opin. Biotechnol. 6: 675–680.

  • Mekle C, Fritsche M, Mundt M, Jähne R and Groner B. . 1998 Gene Therapy 5: 1631–1641.

  • Mukhopadhyay D, Tsiokas L and Sukhatme V. . 1995 Cancer Res. 55: 6161–6165.

  • Mukhopadhyay D, Knebelmann B, Cohen H, Ananth S and Sukhatme VP. . 1997 Mol. Cell. Biol. 17: 5629–5639.

  • Sunahara M, Ichimiya S, Nimura Y, Takada N, Sakiyama S, Sato Y, Todo S, Adachi W, Amano J and Nakagawara A. . 1998 Int. J. Oncol. 13: 319–323.

  • Suzuki K, Hayashi N, Miyamoto Y, Yamamoto M, Ohkawa K, Ito Y, Sasaki Y, Yamaguchi Y, Nakase H, Noda K, Enomoto K, Arai Y, Yamada H, Yoshihara T, Tujimura K, Kawano K, Yoshokawa N and Kamada T. . 1996 Cancer Res. 56: 3004–3009.

  • Weindel K, Marmé D and Weich HA. . 1992 Biochem. Biophys. Res. Commun. 183: 1167–1174.

  • Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R and Kufe D. . 1999 Nature 399: 814–817.

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Acknowledgements

We thank Dr Daniel Caput for the p73α expression plasmid and Dr Maren Mundt for the pGL2-PG13-luc reporter plasmid. We thank Dr Karin Weindel for help with the VEGF-ELISA. Critical reading of the manuscript by Dr Michael Kubbutat and Dr Christoph Sachsenmaier is greatly appreciated. This work was supported by ‘Kirstins Weg e.V.'.

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Authors and Affiliations

  1. Institute of Molecular Medicine, Tumor Biology Center, Breisacher Str. 117, Freiburg, D-79106, Germany

    Dieter Marmé & Günter Finkenzeller

  2. Department of Biochemistry, Manasagangothi Campus, University of Mysore, Mysore, 570006, Karnataka, India

    Bharathi Salimath

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Salimath, B., Marmé, D. & Finkenzeller, G. Expression of the vascular endothelial growth factor gene is inhibited by p73. Oncogene 19, 3470–3476 (2000). https://doi.org/10.1038/sj.onc.1203672

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