p21Ras downstream effectors are increased in activity or expression in mouse liver tumors but do not differ between Ras-mutated and Ras-wild-type lesions

摘要: Mouse liver tumors frequently harbor activating ras gene mutations. Downstream effector molecules of p21Ras include Raf-1 kinase which mediates external signals via signaling pathways to nuclear transcription factors including c-Fos and c-Jun. with differing ras-mutational status were analyzed for alterations in Ras/Raf-1 signal transduction. Tumors characterized respect the presence base substitutions 3 known hot-spot positions at codons 12, 13, 61 Ha-ras, Ki-ras, N-ras. Ha-ras codon or Ki-ras 13 mutations, but no N-ras detected 23 out 33 analyzed, while ras-mutations found 10 tumors. There was significant difference expression p21RaS proteins between ras-mutated without detectable To allow determination activity tumors, a sensitive specific assay developed measurements tissue homogenates. increased about four-fold as compared normal tissue. No differences activity, however, evident ras-wild-type The same true levels c-fos c-jun mRNAs. Moreover, there cell division (5-bromo-2'-deoxyuridine-labeling indices) hepatocytes from similar degree constitutive activation pathway suggests that other within may substitute during oncogenic conversion hepatocytes.