Distinct biological effects are observed in HT-29 colorectal carcinoma cells induced to express K-RASG12V or K-RASG13D

RAS are small membrane-bound GTPase proteins involved in signalling pathways that regulate proliferation, differentiation and apoptosis in all cell types, and whose activating mutations have oncogenic effects. The three major isoforms of p21 RAS (H-, K- and N-RAS) have a high degree of homology, especially in the regions involved in interactions with GDP/GTP and with regulatory proteins and effectors, but differ significantly in the C-terminal 25 amino acids region. This hypervariable domain is the site of posttranslational modifications specific for each isoform, which result in distinct intracellular trafficking routes and final subcellular localizations, where the type and concentration of regulators and effectors may differ.1 This may explain the observed non-overlapping functions of these proteins, the different biological effects of their physiological activation, and their differential involvment, when mutated, in specific tumor types. In almost all cases, the genetic alterations detected in tumoral cells are missense point mutations in codons 12 or 13, more rarely in codon 61, and they always result in a constitutively active protein by inactivating its GTPase activity. Mutations in the K- RAS isoform are a frequent, early event in colorectal tumorigenes