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10.3892/ol.2016.4837

http://scihub22266oqcxt.onion/10.3892/ol.2016.4837
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C4998514!4998514!27602167
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suck abstract from ncbi


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pmid27602167      Oncol+Lett 2016 ; 12 (3): 2222-6
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  • Farnesyl transferase inhibitor FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation #MMPMID27602167
  • Lee KH; Koh M; Moon A
  • Oncol Lett 2016[Sep]; 12 (3): 2222-6 PMID27602167show ga
  • Hyperactive Ras promotes proliferation and malignant phenotypic conversion of cells in cancer. Ras protein must be associated with cellular membranes for its oncogenic activities through post-translational modifications, including farnesylation. Farnesyltransferase (FTase) is essential for H-Ras membrane targeting, and H-Ras, but not N-Ras, has been demonstrated to cause an invasive phenotype in MCF10A breast epithelial cells. In the present study, it was observed that an FTase inhibitor (FTI), FTI-277, blocked epidermal growth factor (EGF)-induced H-Ras activation, but not N-Ras activation in MDA-MB-231 cells, which express wild-type H-Ras and N-Ras. FTI-277 exerted a more potent inhibitory effect on the proliferation of H-Ras-MCF10A cells and Hs578T breast cancer cells expressing an active mutant of H-Ras than that of MDA-MB-231 cells. The invasive/migratory phenotypes of the H-Ras-MCF10A and Hs578T cells were effectively inhibited by FTI-277 treatment. By contrast, FTI-277 did not affect the invasive/migratory phenotypes of MDA-MB-231 cells. However, the EGF-induced invasion of MDA-MB-231 cells was decreased by FTI-277, implicating that FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation. Taken together, the results of the present study suggest that FTase inhibition by FTI-277 may be an effective strategy for targeting H-Ras-mediated proliferation, migration and invasion of breast cells.
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