Effects of Tumor Suppressor Gene (p53) on Brain Tumor Angiogenesis and Expression of Angiogenic Modulators

Victor Tse, Yun Yung, Justin G. Santarelli, David Juan, Michael Hsiao, Martin Haas, Griffith Harsh IV, Gerald Silverberg

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: p53 retarded tumor growth by several known mechanisms, including suppression of cell proliferation and inhibition of tumor angiogenesis. Vascular endothelial growth factors (VEGF) and angiopoietins (Ang-1, Ang-2) are major angiogeneic modulators. The current study examined the effect of p53 on the expression of these factors in conjunction with tumor growth and vascular formation. Materials and Methods: Growth characteristics of rat glioma cells (RT-2) infected with retrovirus (MSCV) encoding a full-length human wild-type p53 gene were examined by clonogenic assay. Expression of the transgene in vitro was verified by RT-PCR and immunoprecipitation. Tumor morphology, vascular architecture and the expression of VEGF, Ang-1, Ang-2 and Tie-2 were examined by immunohistochemistry and semi-quantitative RT-PCR. Results: p53-infected cells showed retardation in growth and colony formation. In vivo, expression of the transgene resulted in prolonged survival and reduction of tumor volume (62%) and reduced the expression of VEGF (57.8%) and Tie-2 (15.4%) but not Ang-1 and Ang-2. The tumor exhibited increased necrosis (38%), hemorrhage and abnormal vascular architecture. Conclusion: p53 causes tumor regression by suppressing tumor proliferation and indirectly induces involution of tumor vessels by fostering unopposed activity of Ang-2 in an environment of diminishing VEGF.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalAnticancer research
Volume24
Issue number1
StatePublished - Jan 2004
Externally publishedYes

Keywords

  • Angiopoietins
  • Gene therapy
  • Glioma
  • p53
  • Retrovirus
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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