title: Genetic background controls tumor development in PTEN-deficient mice.
abstract: PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Germ line mutations of PTEN have been detected in three rare autosomal-dominant disorders. However, identical mutations in the PTEN gene may lead to different symptoms that have traditionally been described as different disorders, such as Cowden disease, Lhermitte-Duclos disease, and Bannayan-Zonana syndromes. This lack of genotype-phenotype correlation prompted us to directly test the possible effects of genetic background or modifier genes on PTEN-controlled tumorigenesis using genetically engineered mouse models. In this study, we generated two animal models in which either exon 5 (Pten(Delta5)) or promoter to exon 3 (Pten(-)) of the murine Pten gene were deleted and compared phenotypes associated with individual mutations on two genetic backgrounds. We found that the onset and spectrum of tumor formation depend significantly on the genetic background but less on the type of mutation generated. Our results suggest that PTEN plays a critical role in cancer development, and genetic background may influence the onset, the spectrum, and the progression of tumorigenesis caused by Pten mutation.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California at Los Angeles School of Medicine, 650 C.E. Young Drive South, Los Angeles, CA 90095, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Freeman
authors.forename: Ralf
authors.initials: R
authors.lastname: Lesche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kertesz
authors.forename: Shungyou
authors.initials: S
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Matthias
authors.initials: M
authors.lastname: Groszer
authors.forename: Hilda
authors.initials: H
authors.lastname: Martinez-Diaz
authors.forename: Nora
authors.initials: N
authors.lastname: Rozengurt
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D000483:Alleles; D000818:Animals; D005260:Female; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse