Prx1敲除对4NQO诱导的小鼠舌癌前病变细胞增殖及转录因子Ets1表达的影响

摘要

目的 检测核增殖抗原Ki67和转录因子Ets1在4-硝基喹啉-1-氧化物(4NQO)诱导的Prx1+/+和Prx1+/-小鼠舌癌前病变模型中的表达,探讨Prx1敲除对小鼠舌癌前病变细胞增殖及转录因子Ets1表达的影响.方法 实验分为Prx1+/+阴性对照组、Prx1+/+4NQO组、Prx1+/-阴性对照组、Prx1+/-4NQO组.在实验过程中对照组小鼠给与蒸馏水,实验组小鼠给与4NQO饮用水,第16周末处死小鼠,取舌组织,用于HE染色及Ki67和Ets1免疫组织化学染色.结果 在4NQO的诱导下,成功构建鼠舌癌前病变模型.组织学检查发现在第16周末,实验组小鼠舌黏膜上皮表现为单纯增生或不同程度的异常增生.免疫组化结果显示,与对照组正常舌黏膜相比,Ki67、Ets1在Prx1+/+ 4NQO组舌癌前病变中表达明显增高(P<0.01).Prx1敲除导致Prx1+/-4NQO组舌黏膜上皮中Ki67、Ets1表达明显降低(P<0.01).结论 Prx1对细胞增殖有促进作用,可能通过调控转录因子Ets1在口腔癌前病变发生发展中发挥重要作用.%Objective To investigate the effect of Prx1 knockout on cell proliferation and transcription factor Ets1 expression in mouse tongue precancerous lesions by detecting the nuclear proliferating antigen Ki67 and transcription factor Ets1 expression in 4-nitroquinoline-1-oxide(4NQO) induced tongue precancerous lesion model in Prx1+/+ and Prx1+/-mice.Methods The experiment included Prx1+/+ negative control group, Prx1+/+ 4NQO group, Prx1+/-negative control group, Prx1+/-4NQO group.The mice in control group were given distilled water while mice in experimental group were given 4NQO water.All mice were sacrificed and the tongues were removed for hematoxylin-eosin(HE) staining and Ki67 and Ets1 immunohistochemistry staining at the end of 16 weeks.Results The mouse tongue precancerous lesion model was constructed with the induction of 4NQO.The epithelium of tongue mucosa in experimental group showed hyperplasia or different degrees of dysplasia at the end of 16 weeks.Ki67 and Ets1 expression in tongue precancerous lesions was significantly increased in Prx1+/+ 4NQO group compared with normal tongue mucosa in control group (P<0.01).Prx1 knockout resulted in significant decrease of Ki67 and Ets1 expression in tongue mucosa in Prx1+/-4NQO group (P<0.01).Conclusion Prx1 promotes cell proliferation and may play an important role in the occurrence and development of oral precancerous lesion by regulating transcription factor Ets1.