Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Sarron Randall-Demllo
,
University of Tasmania, Launceston, TAS, Australia
Ruchira Fernando
,
Launceston General Hospital, Launceston, Australia
Terry Brain
,
Launceston General Hospital, Launceston, Australia
Anthony Cook
,
University of Tasmania, Launceston, Australia
Rajaraman Eri
,
The University of Tasmania, Launceston, TAS, Australia
Patients with ulcerative colitis are at increased risk of developing colorectal cancer. Colitis-associated colorectal cancer (CACC) progresses through similar stepwise gene mutations observed in sporadic cancers, but the sequence in which they occur is reversed. Understanding the transition from colitis to tumour requires relevant animal models. Colonic carcinogenesis has been modelled using genotoxic carcinogens such as azoxymethane. We hypothesised that exacerbation of pre-existing chronic colitis in a Muc2 mutant (
Winnie) mouse strain with dextran sulphate sodium (DSS) would induce colorectal tumourigenesis.
Winnie mice received 1% w/v DSS orally and drinking water interchangeably, each for seven days for a total of 42 days. Colonic segments were collected for histological, immunohistochemical and gene expression evaluation.
Winnies given DSS displayed flat, multifocal dysplasia of the mid-distal colon with 100% penetrance, and progression to adenocarcinoma in 17% of animals. Nuclear accumulation of β-catenin was absent in dysplasia. Preliminary analysis identified differentially expressed genes including Cox2 and neutrophil chemo-attractant Cxcl5.
Exacerbation of colitis in Winnie resulted in exclusively flat colonic dysplasia after 42 days, without a genotoxic carcinogen. This experimental model will be useful for exploring the early changes in the colitis-dysplasia-carcinoma sequence in CACC.
