4 K-ras protooncogene in uman pancreatic cancer

Abstract

This chapter discusses K- ras protooncogene in human pancreatic cancer. It was reported that the human genome contains c-Ha- ras and c-Ki- ras in the 1980s. Consequently, the structure and organization of the K- ras protooncogene were clarified. The ras family contains three members: K- ras , N- ras , and H- ras . Although they have different genetic structures, they all code for proteins of 189 amino acid residues, generically designated as 21 kDa proteins. The p21 ras -encoded proteins bind the guanosine diphosphate (GDP) and guanosine triphosphate (GTP) with high affinity and possess a low intrinsic GTPase activity. The ras gene bound to GTP is maintained in an active configuration that triggers other enzymatic second messengers, leading to nuclear signals and resulting in cellular division and proliferation. The mutated ras protooncogene is not able to convert GTP to inactive GDP, resulting in a constitutively active ras protein product, unregulated cellular proliferation signals, and susceptibility to transformation. Of the ras family, K- ras is the most frequently mutated member in human tumors, especially in human pancreatic cancer.