Format

Send to

Choose Destination
Anticancer Res. 2004 Jan-Feb;24(1):1-10.

Effects of tumor suppressor gene (p53) on brain tumor angiogenesis and expression of angiogenic modulators.

Author information

1
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. vkt@stanford.edu

Erratum in

  • Anticancer Res. 2004 Mar-Apr;24(2C):1325.

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.

PMID:
15015569
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center