title: Revealing the role of SGK1 in the dynamics of medulloblastoma using a mathematical model.
abstract: Deregulation 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.
authors.affiliation: Institute of Applied Mathematics, Interdisciplinary Center for Scientific Computing (IWR) and BIOQUANT, University of Heidelberg, Germany. Electronic address: joanna.kawka@bioquant.uni-hd.de.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kawka
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Sturm
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pleier
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfister
authors.affiliation: Institute of Applied Mathematics, Interdisciplinary Center for Scientific Computing (IWR) and BIOQUANT, University of Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Marciniak-Czochra
mesh_terms: D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008527:Medulloblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D016271:Proto-Oncogene Proteins c-myc; D000099184:Serum-Glucocorticoid Regulated Kinases; C489427:MYC protein, human
keywords: Differential equations; GSK3β; MYC; Wnt signaling pathway