p14^(ARF)、p53抑癌基因与胰腺癌发生、发展的相关研究

Correlative experimental investigation of tumor suppressor gene p14 ARF and p53 on the occurrence and development of pancreatic carcinoma

目的 :研究抑癌基因p14 ARF、p5 3在胰腺癌组织中的表达和胰腺癌细胞株PC 3转染p14 ARF基因前后的生长状况 ,探讨它们对胰腺癌发生、发展的影响。方法 :采用免疫组织化学法检测 10例正常胰腺组织、4 2例胰腺癌组织中p14 ARF蛋白、p5 3蛋白的表达。将外源性p14 ARFcDNA重组质粒pCI neo p14 ARF和空载体质粒pCI neo分别转染入胰腺癌PC 3细胞中 ,观察转染后胰腺癌PC 3细胞株的生长状况。结果 :正常胰腺组织中p14 ARF的表达率为 90 % ,胰腺癌组织中为 35 .7% ;正常胰腺组织中p5 3的表达率为 0 ,胰腺癌组织中为 4 5 .2 %。胰腺癌PC 3细胞的p14 ARF基因呈缺失变异。外源性野生型p14 ARF基因和空载体质粒pCI neo成功转染入PC 3细胞 ,转染p14 ARF基因的胰腺癌细胞株第 1天生长抑制率为 2 2 % ,第 5天为 2 6 %。结论 :抑癌基因p14 ARF蛋白在胰腺癌中低表达 ,突变型p5 3蛋白在胰腺癌中呈高表达 ;转染p14 ARF基因的胰腺癌细胞株生长受到抑制 ;抑癌基因p14 ARF、p5 3对胰腺癌的发生、发展可能产生影响。

Objective:To study the expression of the tumor suppressor gene p14 ARF and p53 in the pancreatic carcinoma tissue and the growing situation after and before p14 ARF gene transfect into pancreatic carcinoma cell line PC-3.To explore the influence of them on the occurrence and development of the pancreatic carcinoma.Methods:The expression of gene p14 ARF and p53 were examined using immunohistochemical technique in 10 cases with normal pancreatic tissues and 42 cases pancreatic carcinoma tissues.The exogenous recombined plasmid pCI-neo-p14 ARF and null vector plasmid pCI-neo were transfected into pancreatic carcinoma cell line PC-3, respectively. MTT assay was used to compare the change of growth curve of PC-3, PC-3/vec and PC-3/ p14 ARF cell.Results:The positive rates of p14 ARF in tissues of normal pancreas and pancreatic carcinoma were 90.0% and 35.7%,respectively.The positive rates of p53 in tissues of normal pancreas and pancreatic carcinoma were 0 and 45.2%, respectively. The p14ARF gene was deleted in pancreatic carcinoma cell line PC-3. The combined plasmed pCI-neonp14 ARF and null vector plasmid pCI-neo were successfully transfected into pancreatic carcinoma cell line PC-3. The growth inhibition rate of PC-3 cell on the 1st and 5 th day after introduction of p14 ARF gene was 22% and 26%, respectively.Conclusion:The positive rates of p14 ARF in the normal pancreas tissues are higher than that in tissues of pancreatic carcinoma. The positive rates of p53 in the normal pancreatic tissues are lower than that of the pancreatic carcinoma tissues. Tumor suppressor gene p14 ARF and p53 are closely related to the occurrence and development of pancreatic carcinoma. The growth of pancreatic carcinoma cell line PC-3 transfected by gene p14 is inhibited.