Bashir, O.; Goodlad, R.A.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA31
Academic Journal
Background: TGF-α may be the main ligand for the EGF receptor in the gut and thus plays an important role in maintaining the integrity of the gastrointestinal tract. TGF-α null mice show some changes in the morphometry of the colon and also have an increased susceptibility to colitis. TGF-α expression is increased in humans with adenomas and autocrine stimulation of the EGF-receptor by TGF-α has been linked to the growth of adenoma cell lines. Aims: To determine if TGF-α knock out lead to altered susceptibility to carcinogen induced colonic tumours. Methods: TGF-α null mice and appropriate wild type mice were either injected with saline or dimethylhydrazine (DMH) For 16 weeks. Two weeks after the last injection they were given BrdU and vincristine and then autopsied. Polyp number, cell proliferation, and crypt fission were then assayed. Results: Small bowel weight was significantly greater in the TGF-α null mice (p < 0.001), but colon weight was not changed. DHM had no effect on small bowel weight but significantly increased colon weight and cell proliferation (p < 0.001). There was a small but nonsignificant reduction in polyp number (7.1±03 v 6.1±0.6 WT/KO) but the number of aberrant crypt foci was reduced from 97.5±7.4 to 53.2±4.1 (p < 0.001) in the null mice. Discussion: TGF-α knock out mice had half the number of aberrant crypt foci of the wild type mice, but polyp number was not altered, suggesting that TGF-α is involved in the initiation rather than the promotional stages of carcinogenesis.


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