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000126835 1001_ $$aKawka, Joanna$$b0
000126835 245__ $$aRevealing the role of SGK1 in the dynamics of medulloblastoma using a mathematical model.
000126835 260__ $$aLondon$$bAcademic Press$$c2014
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000126835 520__ $$aDeregulation of signaling pathways and subsequent abnormal interactions of downstream genes very often results in carcinogenesis. In this paper, we propose a two-compartment model describing intricate dynamics of the target genes of the Wnt signaling pathway in medulloblastoma. The system of nine nonlinear ordinary differential equations accounts for the formation and dissociation of complexes as well as for the transcription, translation and transport between the cytoplasm and the nucleus. We focus on the interplay between MYC and SGK1 (serum and glucocorticoid-inducible kinase 1), which are the products of Wnt/β-catenin signaling pathway, and GSK3β (glycogen synthase kinase). Numerical simulations of the model solutions yield a better understanding of the process and indicate the importance of the SGK1 gene in the development of medulloblastoma, which has been confirmed in our recent experiments. The model is calibrated based on the gene expression microarray data for two types of medulloblastoma, characterized by monosomy and trisomy of chromosome 6q to highlight the difference between diagnoses.
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000126835 650_7 $$2NLM Chemicals$$aImmediate-Early Proteins
000126835 650_7 $$2NLM Chemicals$$aMYC protein, human
000126835 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-myc
000126835 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProtein-Serine-Threonine Kinases
000126835 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aserum-glucocorticoid regulated kinase
000126835 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b1$$udkfz
000126835 7001_ $$0P:(DE-HGF)0$$aPleier, Sabrina$$b2
000126835 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b3$$udkfz
000126835 7001_ $$aMarciniak-Czochra, Anna$$b4
000126835 773__ $$0PERI:(DE-600)1470953-3$$a10.1016/j.jtbi.2014.03.028$$gVol. 354, p. 105 - 112$$p105 - 112$$tJournal of theoretical biology$$v354$$x0022-5193$$y2014
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