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 language | English (US) |
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Pages (from-to) | 1-10 |
Number of pages | 10 |
Journal | Anticancer research |
Volume | 24 |
Issue number | 1 |
State | Published - Jan 2004 |
Externally published | Yes |
Keywords
- Angiopoietins
- Gene therapy
- Glioma
- p53
- Retrovirus
- VEGF
ASJC Scopus subject areas
- Oncology
- Cancer Research