title: Loss of Trp53 promotes medulloblastoma development but not skin tumorigenesis in Sufu heterozygous mutant mice.
abstract: Basal cell carcinoma of the skin typically carries genetic alterations in components of the hedgehog (HH) signaling pathway. Previously, we generated a knockout mouse with a loss-of-function mutation in suppressor of fused (Sufu), an essential repressor of the pathway downstream of Hh ligand cell surface reception. Mice heterozygous for the mutated Sufu allele develop a skin phenotype that includes lesions similar to basaloid follicular hamartomas. The purpose of the current study was to test the possibility that the simultaneous loss of the tumor suppressor gene, transformation related protein 53 (Trp53), would aggravate the Sufu skin phenotype since Trp53 loss is known to enhance the growth of other Hh-driven tumors. Consistent with previous reports, medulloblastomas and rhabdomyosarcomas developed in Sufu(+/-) ;Trp53(-/-) mice. However, the characteristic Sufu(+/-) skin phenotype was not altered in the absence of Trp53, and showed no changes in latency, multiplicity, cellular phenotype, or proliferative capacity of the basaloid lesions. This finding was both novel and intriguing and demonstrated a differential, tissue-specific sensitivity to Sufu and Trp53 tumor suppressor gene loss, which may be linked to developmental stage and the degree of proliferative activity in specific cell types.
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Karin
authors: K
authors: Heby-Henricson
authors: Asa
authors: A
authors: Bergström
authors: Björn
authors: B
authors: Rozell
authors: Rune
authors: R
authors: Toftgård
authors: Stephan
authors: S
authors: Teglund
mesh_terms: D000818:Animals; D002528:Cerebellar Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008527:Medulloblastoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D012097:Repressor Proteins; C490763:Sufu protein, mouse; D016159:Tumor Suppressor Protein p53