Expression of p 21^WAF1/CIP1 in rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Abstract

We investigated immunohistochemical expression of p21^WAF1/CIP1 (p21) and TGF-β in rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4 NQO). The protein p21, which inhibits cell proliferation, is induced by the wild type p53 tumor suppressor protein and by TGF-β. Expression of the p21 protein almost disappeared in tongue epithelial cells at 16 weeks after 4 NQO administration, while it showed overexpression at 24 weeks. TGF-β was found in small amounts at 16 weeks and was expressed strongly at 24 weeks after administration of 4 NQO. Our co-worker previously found that a p53 mutation occurred in the tongue epithelium at 16 weeks using the same model. Therefore, the overexpression of p21 at 24 weeks may be induced by TGF-β. We also found that expression of Ki-67 was decreased at 24 weeks, which we assumed was caused by changes in p21. However, the inhibitory effect of p21 on carcinoma is not adequate to stop carcinogenesis. This study suggests that expression of p21 in the rat tongue changed as a result of carcinogenesis, and that p21 overexpression in carcinoma may be induced by TGF-β.