Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells.
The earliest genetic alteration in human astrocytoma progression is mutation of the p53 tumour suppressor gene, while one of the earliest phenotypic changes is the stimulation of neovascularization. Here, we tested the role of p53 in the angiogenic process by introducing a tetracycline-regulated wild type p53 gene into null glioblastoma cells. The parental cells expressed strong angiogenic activity while upon induction of wild type, but not mutant, p53 expression, the cells secreted a factor able to neutralize the angiogenicity of the factors produced by the parental cells as well as of basic fibroblast growth factor.
Van Meir
E G
EG
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla 92093-0660.
Polverini
P J
PJ
Chazin
V R
VR
Su Huang
H J
HJ
de Tribolet
N
N
Cavenee
W K
WK
D020533:Angiogenesis Inhibitors; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002465:Cell Movement; D003315:Cornea / Q000098:blood supply; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D009363:Neoplasm Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53