The p53 tumor suppressor protein has long been recognized as the central factor 
protecting humans from cancer. It has been famously dubbed "the guardian of the 
genome" due to its ability to respond to genotoxic stress, such as DNA damage 
and other stress signals, and to protect the genome by inducing a variety of 
biological responses including DNA repair, cell cycle arrest, and apoptosis. 
However, the tumor suppressive effects of p53 go far beyond its roles in 
mediating these three processes. There is growing evidence that p53 also exerts 
its effects on multiple aspects of tumor formation, including suppression of 
metastasis and, as summarized in this review, inhibition of new blood vessel 
development (angiogenesis). The p53 protein has been shown to limit angiogenesis 
by at least three mechanisms: (1) interfering with central regulators of hypoxia 
that mediate angiogenesis, (2) inhibiting production of proangiogenic factors, 
and (3) directly increasing the production of endogenous angiogenesis 
inhibitors. The combination of these effects allows p53 to efficiently shut down 
the angiogenic potential of cancer cells. Inactivation of p53, which occurs in 
approximately half of all tumors, reverses these effects; as a consequence, 
tumors carrying p53 mutations appear more vascularized and are often more 
aggressive and correlate with poor prognosis for treatment. Thus, the loss of 
functional p53 during tumorigenesis likely represents an essential step in the 
switch to an angiogenic phenotype that is displayed by aggressive tumors.