Activation of Proto-oncogenes by Mutations
Ras proto-oncogenes
There are three active genes (N, H and K) belonging to the c-rasfamily (found both in man and rat), which give rise to oncogenes. All three genes are related with conserved sequences and some variable regions. The v-H-ras and v-K-ras differ from corresponding c-ras genes by alterations of 3 and 7 amino acids respectively. It has also been shown that each c-ras proto-oncogene can give rise to an oncogene (found in human tumours) by a single base replacement leading to the substitution of a single amino acid at position 12 or 61 in one of the Ras proteins (Table 45.6). It has also been shown that the DNA from a lung carcinoma has a mutant c-ras gene, while DNA from normal tissue of same cancer patient has a wild type c-ras gene. Such observations suggest that a spontaneous mutation in c-ras gene may occur in any tissue leading to tumour formation. The oncogenicity of c-ras genes may also be enhanced by over-expression or amplification of c-ras genes, suggesting that oncogenesis may also depend on over-activity of Ras protein.