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Confirmation of a linkage between H‐Ras and MMP‐13 expression as well as MMP‐9 by chemical genomic approach
Author(s) -
Lee SuKyung,
Kim Jung Min,
Lee MiYoung,
Son KwangHee,
Yeom Young Il,
Kim CheolHee,
Shin Youseung,
Koh Jong Sung,
Han Dong Cho,
Kwon ByoungMog
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21610
Subject(s) - prenylation , matrix metalloproteinase , transferase , angiogenesis , biology , farnesyl diphosphate farnesyltransferase , enzyme , complementary dna , microbiology and biotechnology , gene , biochemistry , cancer research , chemistry , farnesyltransferase
As farnesylation of the Ras protein by farnesyl transferase is a critical step for the Ras functional activity, the farnesyl transferase inhibitor could affect H‐Ras functions and the inhibitors such as arteminolide, SCH66336 and LB42908 completely inhibited Ras‐farnesylation. However, they did not induce apoptosis of H‐Ras‐transformed cells with concentration for blocking H‐Ras farnesylation. To determine the antitumor effects of the inhibitors, it was analyzed through the expression profile of genes, regulated by activated H‐Ras or FTIs by using cDNA microarray. On the basis of the results, the relationship between H‐Ras and MMPs expression was confirmed by RT‐PCR, Western bolt, zymographic analysis and angiogenesis assay. Our results suggested that activation of MMP‐13 as well as MMP‐9 induced by H‐Ras is involved in angiogenesis and with farnesyl transferase inhibitors, in part, exerts their anticancer effects. We confirmed that MMP‐13 is a critical H‐Ras target gene through chemical genomic approaches with farnesyl transferase inhibitors. © 2005 Wiley‐Liss, Inc.