Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis

D. G. Duda, M. Sunamura, L. Lozonschi, T. Yokoyama, T. Yatsuoka, F. Motoi, A. Horii, K. Tani, S. Asano, Y. Nakamura, S. Matsuno

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 functional binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-l expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules.

Original languageEnglish
Pages (from-to)490-496
Number of pages7
JournalBritish Journal of Cancer
Volume86
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Angiogenesis
  • Brain-specific angiogenesis inhibitor 1
  • Tumour p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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