Inactivation of Icmt inhibits lung tumor development in mice with B-RAF-induced lung cancer

dc.contributor.authorLim, Hoo Ching
dc.contributor.departmentChalmers tekniska högskola / Institutionen för kemi- och biotekniksv
dc.contributor.departmentChalmers University of Technology / Department of Chemical and Biological Engineeringen
dc.description.abstractSomatic point mutations of B-RAF are associated with ~8% of human cancer and result in deregulation of the MAPK pathway. Substitution of valine-to-glutamic acid at position 600, B-RAFV600E, accounts for approximately 90% of all B-RAF mutations in human cancer. Isoprenylcysteine carboxyl methyltransferase (ICMT) is an endoplasmic reticulum membranebound protein which catylzes post-translational carboxyl methylation of proteins encoding a C-terminal CAAX motif (C, cystein, A, aliphatic amino acids, X, any amino acid). Previous in vitro studies have shown that inactivation of ICMT might be a potential anticancer drug target. However, no studies have been done to investigate the effect of ICMT deficiency in B-RAF-induced malignancies. In the current study, we evaluated the impact of inactivating Icmt in the pathogenesis of B-RAF-induced lung tumors in mice and thereby validated ICMT as a potential anticancer target. By using a Cre-loxP recombination technique, we simultaneously switched on the expression of ocogenic B-RAFV600E and inactivated the Icmt expression on lung cells and primary mouse embryonic fibroblasts. Inactivation of Icmt significantly reduce the growth of B-RAF-induced lung tumors in mice. In addition, ICMT deficiency blocked B-RAF-induced transformation in primary mouse embryonic fibroblasts. These results indicate that targeting ICMT could be an attractive strategy to treat B-RAF-induced malignancies.
dc.subjectIndustriell bioteknik
dc.subjectIndustrial Biotechnology
dc.titleInactivation of Icmt inhibits lung tumor development in mice with B-RAF-induced lung cancer
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster Thesisen
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