Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice
| Autor: | Nancy E. Kohl, Charles A. Omer, Michael W. Conner, Neville J. Anthony, Joseph P. Davide, S. Jane Desolms, Elizabeth A. Giuliani, Robert P. Gomez, Samuel L. Graham, Kelly Hamilton, Laurence K. Handt, George D. Hartman, Kenneth S. Koblan, Astrid M. Kral, Patricia J. Miller, Scott D. Mosser, Timothy J. O'Neill, Elaine Rands, Michael D. Schaber, Jackson B. Gibbs, Allen Oliff |
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| Rok vydání: | 1995 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Farnesyl Protein Transferase Transgene Farnesyltransferase Antineoplastic Agents Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Mice Methionine Transferases Internal medicine medicine Animals Enzyme Inhibitors chemistry.chemical_classification Farnesyltranstransferase Alkyl and Aryl Transferases Dose-Response Relationship Drug Farnesyl Transferase Inhibitor Farnesyltransferase inhibitor Mammary Neoplasms Experimental General Medicine Salivary Gland Neoplasms Genes ras Enzyme Endocrinology chemistry Cancer research biology.protein Female |
| Zdroj: | Nature Medicine. 1:792-797 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | For Ras oncoproteins to transform mammalian cells, they must be post-translationally modified with a farnesyl group in a reaction catalysed by the enzyme farnesyl-protein transferase (FPTase). Inhibitors of FPTase have therefore been proposed as anti-cancer agents. We show that L-744,832, which mimics the CaaX motif to which the farnesyl group is added, is a potent and selective inhibitor of FPTase. In MMTV-v-Ha-ras mice bearing palpable tumours, daily administration of L-744,832 caused tumour regression. Following cessation of treatment, tumours reappeared, the majority of which regressed upon retreatment. No systemic toxicity was found upon necropsy of L-744,832-treated mice. This first demonstration of anti-FPTase-mediated tumour regression suggests that FPTase inhibitors may be safe and effective anti-tumour agents in some cancers. |
| Databáze: | OpenAIRE |
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