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.
BACKGROUND:p53retarded 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 ratglioma 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.
Authors: Amy Sun; Lewis Hou; Tiffany Prugpichailers; Jason Dunkel; Maziyar A Kalani; Xiaoyuan Chen; M Yashar S Kalani; Victor Tse Journal: Neurosurgery Date: 2010-04 Impact factor: 4.654
Authors: Elizabeth Scribner; James R Hackney; Hannah C Machemehl; Reina Afiouni; Krishna R Patel; Hassan M Fathallah-Shaykh Journal: J Neurooncol Date: 2017-04-27 Impact factor: 4.130