TP53 and Cowden disease: PTEN encodes a lipid phosphatase which antagonizes PI3K, and these two genes are often lost in many human cancers.35,443 Further, mutated PTEN are discovered in rare autosomal dominant cancer susceptibility syndromes, such as Cowden’s disease.444 The gene p53 deleted, point mutated and allele lost are common in most human cancers.445,446 p53 mutation is also related to Li Fraumeni syndrome which is susceptible to hereditary cancer.253 Therefore, Rb, E2F, PTEN, PI3K, AKT, and p53 are all involved in the function of cell growth, and gain or loss function of TSGs and oncogene.