title: The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis.
abstract: OBJECTIVE
  Differences in genetic background may play a role in the development of ulcerative colitis (UC)-related neoplasia. Loss of heterozygosity (LOH) of APC has been reported in human UC-associated neoplasia. To investigate the role of genetic differences in UC-associated neoplasia, we compared differences in dextran sodium sulfate (DSS) colitis-associated neoplasia between wild-type C57BL/6J mice (WT-DSS) and C57BL/6J mice with a germline mutation in Apc (Min-DSS).
  
  
  METHODS
  DSS colitis was induced in female wild-type and Min mice. Age- and sex-matched non-DSS-treated Mins were also studied. Animals were sacrificed after 1 and 2 cycles of DSS. The cecums and large intestines were studied for numbers of dysplasias/cancers. Dysplasias were studied for LOH of Apc.
  
  
  RESULTS
  No WT-DSS, 100% of Min-DSS, and 50% of non-DSS-treated Mins had dysplasia. The mean numbers of lesions per mouse were 0 (WT-DSS), 15.6 and 29.3 (1 and 2 cycles Min-DSS, respectively), 1.2 and 1.9 (age-matched control Min, 1 and 2 cycle equivalents, respectively; P < 0.0002, Min-DSS vs. WT-DSS and non-DSS-treated Min; P = 0.03, Min-DSS 2 cycle vs. Min-DSS 1 cycle). Cancers were seen in 0%, 22%, and 40% of non-DSS Min, Min-DSS-1 cycle, and Min-DSS-2 cycle animals, respectively. LOH of Apc was observed in 90.6% of dysplasias and 6% of nondysplastic mucosa.
  
  
  CONCLUSIONS
  A germline mutation in Apc contributes significantly to the development of colitis-associated neoplasia. Colitis markedly accelerates the development of dysplasia and cancer in the Min mouse. Dysplasia in Min-DSS occurs through LOH of Apc.
authors.affiliation: Department of Pathology, Division of Medical Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. hs_cooper@fccc.edu
authors.forename: H S
authors.initials: HS
authors.lastname: Cooper
authors.forename: L
authors.initials: L
authors.lastname: Everley
authors.forename: W C
authors.initials: WC
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Pfeiffer
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Murthy
authors.forename: M L
authors.initials: ML
authors.lastname: Clapper
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D003108:Colonic Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016264:Dextran Sulfate; D005260:Female; D017491:Genes, APC; D018095:Germ-Line Mutation / Q000502:physiology*; D015994:Incidence; D019656:Loss of Heterozygosity; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D014456:Ulcer / Q000235:genetics / Q000473:pathology
chemical_list: D016264:Dextran Sulfate