目的观察丝裂原活化蛋白激酶磷酸酶-1(MKP-1)在人胰腺癌组织中的表达。方法收集手术切除人胰腺癌组织、慢性胰腺炎(cP)组织和正常胰腺组织标本各20例,分别采用Northern blot法及Western blot法检测MKP-1在3种组织中的表达情况,并采用Western blot法进一步验证MKP-1在6株胰腺癌细胞株中的表达情况。结果Northern blot检测结果显示,20例正常胰腺组织标本中,有7例(35%)存在MKP-1mRNA弱表达,13例(65%)表达极弱甚至不表达;20例cP组织标本中,7例(35%)存在MKP-1mRNA中至高水平表达;20例胰腺癌组织标本中,12例(60%)存在MKP-1mRNA高表达,8例(40%)为低到中等水平表达。半定量分析结果显示,与正常胰腺组织相比,胰腺癌组织中MKP-1mRNA平均表达水平升高了8.1倍(P=0.016),CP中MKP-1mRNA的表达水平升高了6.2倍(P=0.035);胰腺癌与CP组织的MKP-1mRNA表达水平差异没有统计学意义(P=0.442)。Western blot检测结果显示,胰腺癌组织中MKP—1蛋白表达水平也明显高于正常胰腺组织;在6株胰腺癌细胞株中均检测到MKP-1的表达,除胰腺癌CAPAN-1细胞株表达略低外,其余5株胰腺癌细胞均呈高表达。结论在CP组织、胰腺癌组织及胰腺癌细胞株中均存在MKP-1高表达,MKP-1可能参与了胰腺癌细胞的早期发生过程。
Objective To evaluate the expression of mitogen activated protein kinase phosphatase- 1 ( MKP- 1 ) in pancreatic cancer. Methods Totally 60 cases of normal pancreas, chronic pancreatitis ( CP), and pancreatic cancer tissues were collected by operation in our hospital. Pancreatic tissues were analyzed by Northern blot analysis and Western blot analysis. Meanwhile, MKP-1 expression was detected in 6 pancreatic cancer cell lines by Western blot analysis. Results Northern blot analysis of total RNA revealed relatively low MKP-1 mRNA expression in 7 of 20 ( 35% ) normal pancreatic samples. In the remaining 13 samples, the MKP-1 mRNA was absent to faint detectable. In 7 of the 20 CP samples, MKP-1 was demonstrated moderate to high expression. In contrast, 12 of 20 (60%) pancreatic cancer samples MKP-1 mRNA was expressed at high levels, whereas in the remaining 8 Cancer tissues this mRNA moiety was present at low to moderate levels. Densitometric analysis with normalization to 7S revealed that the median level of MKP-1 mRNA in CP and cancerous tissues was increased by 6. 2 folds (P =0. 035) and 8. 1 folds (P =0. 016) in comparison with the median level in the normal pancreatic samples, respectively. Overexpression of MKP- 1 was also found in 6 pancreatic cancer cell lines, in which the expression of MKP-1 was slightly lower in one pancreatic cancer cell line but high in the remaining 5 cell lines. Conclusions MKP-1 is over-expressed in pancreatic cancer, CP tissues, and pan- creatic cell lines. It is speculated that MKP-1 may play an important role in tumorigenesis of pancreatic cancer.