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-1 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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Duda DG,Sunamura M,Lozonschi L,Yokoyama T,Yatsuoka T,Motoi F,Horii A,Tani K,Asano S,Nakamura Y,Matsuno Sdoi
10.1038/sj.bjc.6600067subject
Has Abstractpub_date
2002-02-01 00:00:00pages
490-6issue
3eissn
0007-0920issn
1532-1827journal_volume
86pub_type
杂志文章abstract::The purpose of the study is to test the hypothesis that expression of cell cycle regulatory proteins p16(INK4a) and pRb is significantly associated with prognosis in ovarian carcinomas. We performed immunohistochemical analysis of p16(INK4a) and pRb expression and correlated with survival in a series of 300 patients w...
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