大鼠胰腺癌和非癌胰腺组织中EZH_2和PTEN的表达及其意义

Expression and significance of EZH_2 and PTEN in pancreatic cancer and non-cancerous pancreatic tissues in rats

目的探讨大鼠胰腺癌和非癌胰腺组织中EZH2和PTEN的表达水平及其在胰腺癌发生中所起的作用。方法将二甲基苯荓蒽（DMBA）直接置入胰腺实质内制备胰腺癌模型（A,B组）,B组成模1周后每周腹腔注射曲古霉素A（TSA）1μg,A,B组3~5个月内处死,对照组（C组）于第5个月处死;肉眼检查和镜下观察胰腺癌发生情况。EnVisionTM免疫组化法检测3组EZH2和PTEN的表达。结果（1）A组3~5个月癌发生率为48.7%（18/37）,17例为胰腺导管腺癌,1例为纤维肉瘤;B组3~5个月癌发生率为33.3%（12/36）,11例为胰腺导管腺癌,1例为纤维肉瘤;A组胰腺癌最大径均值大于B组（P〈0.05）;C组胰腺和A,B,2组胰腺外主要脏器均未见明显病理改变。（2）A,B组胰腺导管腺癌EZH2表达阳性率明显高于相应非癌胰腺组织（P〈0.01）;A组＋B组胰腺导管癌PTEN表达阳性率明显低于A组＋B组非癌胰腺组织（P〈0.05）,但A组和B组胰腺导管癌PTEN表达阳性率与A组或B组非癌胰腺组织间差异无统计学意义（P〉0.05）;EZH2阳性表达和/或PTEN阴性表达的非癌胰腺组织导管上皮均呈轻至重度不典型增生;胰腺导管癌中EZH2与PTEN表达呈明显不一致性（P=0.045）;C组正常胰腺EZH2表达均阴性而PTEN表达均阳性。2例纤维肉瘤EZH2和PTEN表达均阴性。结论较大剂量DMBA置入胰实质内可获得较高胰腺癌发生率,TSA能抑制胰腺癌的发生和生长;EZH2基因的激活及PTEN基因的失活在大鼠胰腺癌发生中可能起关键作用。

Objective To study the expressive levels of EZH2 and PTEN in pancreatic cancer and non-cancerous tissue,and the effects on carcinogenesis of rat pancreas.Methods dimethylbenzathracene（DMBA） was directly implanted into the parenchyma of rat pancreas（group A,group B）.The rats of group B were treated with 1 mL trichostatin A（TSA） solution（1μg/mL） intravenously per weer 1 week after the model were set up.The rats of group A,B were killed within 3-5 months and the rats in the control（C group） were executed at 5 months to observe the develope of pancreatic cancer by macrograph and microscopy,The EnVisionTM immunohistochemistry was used to assay the expression of EZH2 and PTEN in above pancreatic specimens.Results（1） The incidence of pancreatic cancer within 3-5 months in group A was 48.7%（18/37）,including 17 cases of ductal adenocarcinoma and 1 case of fibrosarcoma.The incidence of pancreatic cancer in group B was 33.3%（12/36）,including 11 cases of ductal adenocarcinoma and 1 cases of fibrosarcoma.The mean maximal diameter of mass was significantly higher in group A than that in group B（P 0.05）.No pathological changes were found in pancreas of group C or other main organs of group A and group B.（2） the positive rxpression rates of EZH2 were significantly higher in ductal adenocarcinoma of group A ＋ group B than those in non-cancerous pancreatic tissues（P 0.01）.The positive expression rate of PTEN was significantly lower in ductal adenocarcinoma in group A ＋ group B than that in non-cancerous pancreatic tissues（P 0.05）.But no stastical difference was found among the positive rate of PTEN in ductal adenocarcinoma of group A or group B and in non-cancerous pancreatic tissues of group A or group B（P 0.05）.The non-cancerous pancreatic tissues with positive expression of EZH2 and/or negative expression of PTEN showed mild to severe atypical hyperplasia of ductal epithelium.An inconsistency was found between the expression of EZH2 and PTEN in ductal adenocarcinoma（P =0.045）.Pancreas of group C showed negative expression of EZH2 and positive expression of PTEN.Two cases of fibrosarcoma showed negative expression of EZH2 and PTEN.Conclusions By use of higher dose of DMBA directly implanted into the parenchyma of pancreas,high incidence of pancreatic cancer can be obtained.TSA could have an inhibitive effect on carcinogenesis and growth of pancratic cancer.The activation of EZH2 gene and inactivation of PTEN gene might have Key effects on pancreas carcinogenesis induced by DMBA in rat.