Regulation of collagen-derived antiangiogenic factors by p53.
BACKGROUND
Evidence suggests that the p53 tumor suppressor protein functions, in part, by limiting tumor angiogenesis. This effect is partly mediated by the ability of p53 to increase production of endogenous angiogenesis inhibitors, such as the collagen-derived antiangiogenic factors (CDAFs), endostatin and tumstatin.


OBJECTIVE
To review the clinical and therapeutic implications of CDAFs and their regulation by p53.


METHODS
We highlight the inhibitory role of CDAFs in angiogenesis and summarize evidence that p53 regulates the transcriptional program leading to their expression, synthesis, assembly and activation.


CONCLUSIONS
The p53 gene is mutated in half of all human tumors and such cancers would be predicted to produce lower levels of CDAFs. We therefore believe that p53 function can be partially compensated by therapeutic use of CDAFs, which offers a promising new avenue for cancer treatment.
McGill University, McGill Cancer Center, 3655 Promenade Sir William Osler, Montreal, QC, Canada.
Sarah
S
Assadian
Jose G
JG
Teodoro
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D019393:Arrestin / Q000737:chemistry; D001324:Autoantigens / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D024141:Collagen Type IV / Q000737:chemistry; D043169:Endostatins / Q000737:chemistry; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry; D009363:Neoplasm Proteins / Q000737:chemistry; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D019393:Arrestin; D001324:Autoantigens; C502625:COL4A2 protein, human; D024141:Collagen Type IV; D043169:Endostatins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C057112:type IV collagen alpha3 chain; C076744:cytoplasmic linker protein 170; D003094:Collagen