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- Title
Kit K641E oncogene up-regulates Sprouty homolog 4 and Trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumours.
- Authors
Gromova, Petra; Ralea, Sebastian; Lefort, Anne; Libert, Frédérick; Rubin, Brian P; Erneux, Christophe; Vanderwinden, Jean-Marie
- Abstract
Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the KitK641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43, Gpc6, Gpr133, Pacrg, Pde3a, Prkar2b, Prkcq/Pkce, Rasd2, Spry4 and Tpbg/5T4 were found to be up-regulated. The proteins encoded by Gja1/Cx43, Pde3a, Prkcq/Pkce were localized in Kit-ir ICC in wild-type and KitK641E animals while Spry4 and Tpbg/5T4 were detected in Kit-ir cells only in KitK641E, but not in KitWT/WT animals. Most up-regulated genes in this mouse model belong to the gene expression profile of human GIST but also to the profile of normal Kit+ ICC in the mouse small intestine. Spry4 and Tpbg/5T4 may represent candidates for targeted therapeutic approaches in GIST with oncogenic KIT mutations.
- Subjects
PROTEIN-tyrosine kinases; GASTROINTESTINAL stromal tumors; GLYCOPROTEIN synthesis; LABORATORY mice; GENE expression; TROPHOBLASTIC tumors; CELL physiology; GENETIC mutation; GENETICS
- Publication
Journal of Cellular & Molecular Medicine, 2009, Vol 13, Issue 8a, p1536
- ISSN
1582-1838
- Publication type
Article
- DOI
10.1111/j.1582-4934.2009.00768.x