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

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
A KalkuhlM Schwarz

Abstract

Mouse liver tumors frequently harbor activating ras gene mutations. Downstream effector molecules of p21Ras include Raf-1 kinase which mediates external signals via kinase signaling pathways to nuclear transcription factors including c-Fos and c-Jun. Mouse liver tumors with differing ras-mutational status were analyzed for alterations in Ras/Raf-1 signal transduction. Tumors were characterized with respect to the presence of base substitutions in the 3 known hot-spot positions at codons 12, 13, and 61 of Ha-ras, Ki-ras, and N-ras. Ha-ras codon 61 or Ki-ras codon 13 mutations, but no N-ras mutations, were detected in 23 out of 33 tumors analyzed, while no ras-mutations were found in 10 of the tumors. There was no significant difference in the expression of p21RaS proteins between ras-mutated tumors and tumors without detectable ras mutations. To allow for determination of Raf-1 kinase activity in tumors, a sensitive and specific assay was developed for measurements with tissue homogenates. Raf-1 kinase activity was increased about four-fold in liver tumors as compared with normal liver tissue. No significant differences in kinase activity, however, were evident between ras-mutated and ras-wild-type tumors. The same was true with...Continue Reading

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Citations

Mar 18, 2000·Toxicology Letters·M SchwarzK Bock
Jul 18, 2008·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Leonhard MohrJack R Wands
Apr 3, 2015·European Journal of Clinical Investigation·Bénédicte Delire, Peter Stärkel
Dec 14, 2004·Oncogene·Maike JaworskiMichael Schwarz
Jan 18, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Marcus A JacksonJune K Dunnick

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