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http://dx.doi.org/10.5352/JLS.2010.20.2.202

Suppresion of Ras Oncogenic Activity by Farnesyl Transferase Inhibitors, YH3938 and YH3945  

Oh, Myung-Ju (Department of Nanomedical Engineering, Pusan National University)
Kim, Nong-Yeon (Department of Nanomedical Engineering, Pusan National University)
Lim, Su-Eun (Department of Nanomedical Engineering, Pusan National University)
Chung, Young-Hwa (Department of Nanomedical Engineering, Pusan National University)
Jhun, Byung-H. (Department of Nanomedical Engineering, Pusan National University)
Publication Information
Journal of Life Science / v.20, no.2, 2010 , pp. 202-207 More about this Journal
Abstract
Ras genes are responsible for up to 30% of human tumor mutations and are composed of three isoforms: H-Ras, K-Ras and N-Ras. The post-translational modification of the CAAX motif of the Ras protein is essential in Ras actions. In the present study, we studied the effects of novel farnesyl transferase inhibitors (FTIs), YH3938 and YH3945, on the actions of oncogenic mutants of H-Ras, K-Ras and N-Ras. YH3938 and YH3945 completely reverted the proliferation and morphology of oncogenic H-Ras-transformed Rat2 cells, but not of oncogenic K-Ras-transformed Rat2 cells. Oncogenic N-Ras-transformed Rat2 cells were slightly affected. Activation of SRE promoters by oncogenic H-Ras and N-Ras, but not by K-Ras, were inhibited by treatment with YH3938 and YH3945. Using bandshift analysis, YH3938 suppressed the processing of oncogenic H-Ras and N-Ras, but not that of oncogenic K-Ras protein. YH3945 only inhibited the processing of H-Ras. From these results, we conclude that YH3938 and YH3945 specifically inhibit actions of oncogenic H-Ras through inhibition of its farnesylation, that YH3938 also inhibits N-Ras activity in a dose-dependent manner, and that these drugs have no effect on oncogenic K-Ras activity.
Keywords
Ras; farnesyl transferase; proliferation; SRE promoter;
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