title: Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development.
abstract: Malignant rhabdoid tumors (MRTs) are rare, aggressive cancers occuring in young children primarily through inactivation of the SNF5(INI1, SMARCB1) tumor suppressor gene. We and others have demonstrated that mice heterozygous for a Snf5 null allele develop MRTs with partial penetrance. We have also shown that Snf5(+/-) mice that lack expression of the pRb family, due to TgT121 transgene expression, develop MRTs with increased penetrance and decreased latency. Here, we report that altering the genetic background has substantial effects upon MRT development in Snf5(+/--) and TgT121 ;Snf5(+/-) mice, with a mixed F1 background resulting in increased latency and the appearance of brain tumors. We also report the establishment of the first mouse MRT cell lines that recapitulate many features of their human counterparts. Our studies provide further insight into the genetic influences on MRT development as well as provide valuable new cell culture and genetically engineered mouse models for the study of CNS-MRT etiology.
authors.affiliation: UNC-Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA. weissman@med.unc.edu
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: E Lorena
authors.initials: EL
authors.lastname: Mora-Blanco
authors.forename: Fatima
authors.initials: F
authors.lastname: Banine
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Rogers
authors.forename: Christopher
authors.initials: C
authors.lastname: Fletcher
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
authors.forename: Charles W M
authors.initials: CW
authors.lastname: Roberts
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Weissman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D059785:Karyotype; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018335:Rhabdoid Tumor / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse