大鼠胰腺癌和非癌胰腺组织中EZH 2和PTEN的表达及其意义
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杨竹林E-mail:yang zhulin8@sina.com

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Expression and significance of EZH 2 and PTEN in pancreatic cancer and non-cancerous pancreatic tissues in rats
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    摘要:

    目的:探讨大鼠胰腺癌和非癌胰腺组织中EZH 2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)1 μg,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。EnVision TM免疫组化法检测3组EZH 2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EZH 2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);EZH 2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EZH 2与PTEN表达呈明显不一致性(P=0.045);C组正常胰腺EZH 2表达均阴性而PTEN表达均阳性。2例纤维肉瘤EZH 2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;EZH 2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。

    Abstract:

    Objective:To study  the expressive levels of EZH 2 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 EnVision TM immunohistochemistry was used to assay the expression of EZH 2 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 EZH 2  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 EZH 2 and/or negative expression of PTEN showed mild to severe atypical hyperplasia of ductal epithelium. An inconsistency was found between the expression of EZH 2 and PTEN in ductal adenocarcinoma(P=0.045). Pancreas of group C showed negative expression of EZH 2 and positive expression of PTEN. Two cases of fibrosarcoma showed negative expression of EZH 2 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 EZH 2 gene and inactivation of  PTEN gene might have key effects on  pancreas carcinogenesis induced by DMBA in rat.

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李清龙|杨乐平|苗雄鹰|杨竹林.大鼠胰腺癌和非癌胰腺组织中EZH 2和PTEN的表达及其意义[J].中国普通外科杂志,2010,19(3):250-254.
DOI:10.7659/j. issn.1005-6947.2010.03.005

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  • 收稿日期:2009-12-11
  • 最后修改日期:2010-02-28
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  • 在线发布日期: 2010-03-15