Short Report J RNAi Gene Silenc (June 2009), 5(1), 339-344 doi: jrgsxx Published online: 20 February 2009 Full Text: (html | pdf ~804kb | refs) Selective RNAi-mediated inhibition of mutated c-kit Irene Ruano and Marta Izquierdo* Centro de Biología Molecular Severo Ochoa, CSIC /UAM, Universidad Autónoma de Madrid, Departamento de Biología Molecular, C/ Nicolás Cabrera, 1 Campus de Cantoblanco, Madrid, Spain *Correspondence to:: Marta Izquierdo, Email: mizquierdo@cbm.uam.es, Tel: +34 911964569, Fax: +34 911964420 Received: 22 December 2008, Revised: 02 February 2009, Accepted: 05 February 2009 © Copyright The Authors ----------------------------------------------------------------------------------------------------------------- ABSTRACT The proto-oncogene c-kit plays an important role in the development and survival of mast cells. Gain-of-function mutations in c-kit are one of the most characteristic events in mast cell leukemia (MCL) but as yet there is no clinically approved treatment for the disease. Here we describe growth inhibition of human MCL cell lines by the use of RNAi against c-kit or its mutant form. Retroviral transduction of HMC1.1 and HMC1.2 cell lines with vectors carrying DNA to be transcribed to RNAi against the wild type or mutant c-kit messengers reduced Kit protein levels considerably, decreased cell proliferation, and increased the apoptotic levels five days after retroviral infection. Thus RNAi targeted against Kit or its mutant form could be considered as a new antiproliferative agent against human mast leukemia cell lines, especially HMC1.2 cells which are resistant to the Kit tyrosine kinase inhibitor, imatinib mesylate. KEYWORDS: RNAi, c-kit, allelic discrimination, mast cell leukemia (MCL), apoptosis ----------------------------------------------------------------------------------------------------------------- Privacy | Disclaimer |