AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis. AIM: To investigate the role of epidermal growth factor receptor (EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib. METHODS: Sprague-Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol, ic) followed by 6 wk later by reactivation with TNBS (5 mg / kg, iv) for 3 d.To induce colitis-associated dysplasia, rats then received TNBS (iv) twice a week for 10 weeks .One group received erlotinib (10 mg / kg , ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after (21 d); the rest received the vehicle. After rats were euthanized, the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1 / 2 and c-Myc .RESULTS: Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon. Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon (50.00% ± 11.47% vs 90.00% ± 10.00% in proximal, P <0.05; 15.00% ± 8.19% vs 50.00% ± 16.67% in mid, P <0.05; and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal, P <0.01) .Erlotinib-treated animals also had reduced cell proliferation, reduced active Erk1 / 2, and reduced c-Myc in colon-vey compared to the vehicle-treated animals.In vitro, erlotinib treatment was shown to markedly decrease c-Myc and pErk1 / 2 levels in rat epithelial cells. Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib (P <0.05). CONCLUSION: Erlotinib can decrease the development of colitis-associated dysplasia, suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.