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Enhanced expression of vascular endothelial growth factor (VEGF) plays a critical role in the tumor progression potential induced by simian virus 40 large T antigen

Oncogene volume 21, pages 2896–2900 (2002)Cite this article

Abstract

Vascular endothelial growth factor (VEGF), an important angiogenic factor, regulates cell proliferation, differentiation, and apoptosis through activation of its tyrosine-kinase receptors, such as Flt-1 and Flk-1/Kdr. Human malignant mesothelioma cells (HMC), which have wild-type p53, express VEGF and exhibit cell growth increased by VEGF. Here, we demonstrate that early transforming proteins of simian virus (SV) 40, large tumor antigen (Tag) and small tumor antigen (tag), which have been associated with mesotheliomas, enhanced HMC proliferation by inducing VEGF expression. SV40-Tag expression potently increased VEGF protein and mRNA levels in several HMC lines. This effect was suppressed by the protein synthesis inhibitor, cycloheximide. Inactivation of the VEGF signal transduction pathway by expression of soluble form of Flt-1 inhibited Flk-1/Kdr activation and HMC proliferation induced by SV40 early genes. Experiments with SV40 mutants revealed that SV40-Tag, but not -tag, is involved in the VEGF promoter activation. However, concomitant expression of SV40-tag enhanced Tag function. In addition, SV40-Tag expression sustained VEGF induction in colon carcinoma cell line (CCL)-233, which have wild-type p53, but not in CCL-238, which lack functional p53. These data indicate that VEGF regulation by SV40 transforming proteins can represent a key event in SV40 signaling relevant for tumor progression.

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References

  • Bocchetta M, Di Resta I, Powers A, Fresco R, Tosolini A, Testa JR . 2000 Proc. Natl. Acad. Sci. USA 97: 10214–10219

  • Browne K . 2001 Ann. Occup. Hyg. 45: 327–329

  • Carbone M, Pass HI, Rizzo P, Marinetti M, Di Muzio M, Mew DJ, Levine AS, Procopio A . 1994 Oncogene 9: 1781–1790

  • Carbone M, Rizzo P, Grimley PM, Procopio A, Mew DJ, Shridhar V, de Bartolomeis A, Esposito V, Giuliano MT, Steinberg SM, Levine AS, Giordano A, Pass HI . 1997 Nat. Med. 3: 908–912

  • Claudio PP, Stiegler P, Howard CM, Bellan C, Minimo C, Tosi GM, Rak J, Kovatich A, De Fazio P, Micheli P, Caputi M, Leoncini L, Kerbel R, Giordano GG, Giordano A . 2001 Cancer Res. 61: 462–468

  • De Luca A, Baldi A, Esposito V, Howard CM, Bagella L, Rizzo P, Caputi M, Pass HI, Giordano GG, Baldi F, Carbone M, Giordano A . 1997 Nat. Med. 3: 913–916

  • DeCaprio JA . 1999 Biologicals 27: 23–28

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

  • Gaetano C, Catalano A, Illi B, Felici A, Minucci S, Palumbo R, Facchiano F, Mangoni A, Mancarella S, Muhlhauser J, Capogrossi MC . 2001 Circ. Res. 88: E38–E47

  • Gonin S, Diaz-Latoud C, Richard MJ, Ursini MV, Imbo A, Manero F, Arrigo AP . 1999 Oncogene 18: 8011–8023

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

  • Kumar-Singh S, Weyler J, Martin MJ, Vermeulen PB, Van Marck E . 1999 J. Pathol. 189: 72–78

  • Orengo AM, Spoletini L, Procopio A, Favoni RE, De Cupis A, Ardizzoni A, Castagneto B, Ribotta M, Betta PG, Ferrini S, Mutti L . 1999 Eur. Respir. J. 13: 527–534

  • Pal S, Datta K, Mukhopadhyay D . 2001 Cancer Res. 61: 6952–6957

  • Paley EL . 1996 Carcinogenesis 17: 939–945

  • Procopio A, Strizzi L, Vianale G, Betta P, Puntoni R, Fontana V, Tassi G, Gareri F, Mutti L . 2000 Genes Chromosomes Cancer 29: 173–179

  • Romano M, Catalano A, Nutini M, D'Urbano E, Crescenzi C, Claria J, Davi G, Procopio A . 2001 FASEB J. 15: 2326–2336

  • Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G, Procopio A . 2001 J. Pathol. 193: 468–475

  • Takayama K, Ueno H, Nakanishi Y, Sakamoto T, Inoue K, Shimizu K, Oohashi H, Hara N . 2000 Cancer Res. 60: 2169–2177

  • Zhang L, Yu D, Hu M, Xiong S, Lang A, Ellis LM, Pollock RE . 2000 Cancer Res. 60: 3655–3661

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Acknowledgements

This work was presented in part at the International Conference on Malignant Mesothelioma-Therapeutic Options and role of SV40: An Update, Chicago, Illinois (USA), April, 2001. It was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and from the Italian Ministero dell' Università e della Ricerca Scientifica (ex 60%) to A Procopio. A Catalano was supported by a fellowship from FIRC. We thank Dr G Finkenzeller and Dr J Abraham for making the VEGF promoter construct, Dr MC Capogrossi for providing the adenovirus vectors, Dr G Vianale and Dr Strizzi for technical assistance and Dr M Bocchetta for providing the SV40 plasmids.

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Authors and Affiliations

  1. Institute of Experimental Pathology, University of Ancona, Faculty of Medicine, Via Ranieri, Ancona, 60131, Italy

    Alfonso Catalano & Antonio Procopio

  2. Department of Human Pathology, University of Messina, Messina, 98125, Italy

    Mario Romano

  3. Department of Oncology and Neuroscience, ‘G. D'Annunzio’ University, Chieti, Italy

    Stefano Martinotti

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  1. Alfonso Catalano
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  4. Antonio Procopio
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Correspondence to Antonio Procopio.

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Catalano, A., Romano, M., Martinotti, S. et al. Enhanced expression of vascular endothelial growth factor (VEGF) plays a critical role in the tumor progression potential induced by simian virus 40 large T antigen. Oncogene 21, 2896–2900 (2002). https://doi.org/10.1038/sj.onc.1205382

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