In:
International Journal of Cancer, Wiley, Vol. 118, No. 9 ( 2006-05), p. 2172-2181
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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