食管癌p63mRNA及MDM-2的表达及其分子机制

Expressions of p63 mRNA and murine double minute 2 in esophageal cancer and molecular mechanisms involved

目的探讨p63mRNA、MDM-2蛋白在食管鳞癌中的表达及其在食管鳞癌形成和预后中的意义。方法采用RT-PCR和免疫组化技术分别检测38例食管鳞癌组织及其对应的正常组织中p63mRNA和MDM-2蛋白的表达水平。结果ΔNp63mRNA在食管鳞癌组织和正常组织中阳性检出率分别为63.15%和52.63%,二者比较无显著性差异;其中低分化食管鳞癌组ΔNp63mRNA的阳性表达率显著高于高/中分化食管鳞癌组,而与年龄、性别、淋巴结转移和临床分期无关。38例食管鳞癌组织中仅有1例呈TAp63 mRNA阳性表达,正常组织样品中未检出有TAp63 mRNA阳性表达。MDM-2蛋白在食管鳞癌组织中的阳性表达率为65.79%,显著高于正常组织,低分化食管鳞癌组MDM-2蛋白的阳性表达率显著高于高/中分化组,而且随临床分期的程度增高而阳性表达率升高,而与年龄、性别、淋巴结转移无关。随着MDM-2蛋白表达率的增加,ΔNp63mRNA的表达率相应增加,二者的表达呈正相关。结论p63基因在食管鳞癌和食管上皮中表达的亚型主要是ΔNp63,ΔNp63参与了食管鳞癌的发生、发展,并与食管鳞癌的预后相关;TAp63不是食管鳞癌和食管上皮中主要的表达亚型,与食管鳞癌的形成基本无关;MDM-2蛋白的表达异常在食管鳞癌形成中起重要作用,而且与鳞癌的预后相关;ΔNp63通过MDM-2发挥其对细胞周期及凋亡的调节作用,进而导致食管鳞癌的形成是其主要的分子机制。

Objective To explore the expressions and the roll of p63mRNA and murine double minute 2 （MDM-2 ） protein in esophageal squamous cell cancer and the prognosis of the cancer. Methods The expressions of p63mRNA and MDM-2 protein in 38 cases of esophageal squamous cell carcinoma tissues and the corresponding esophageal normal tissues were detected using reverse transcriptase poly- merase chain reaction （ RT-PCR） and immunohistochemistry. Results The positive rates of deltaNp63 mRNA in all malignant and normal tissues were 63.5% and 52.63% respectively,without significant difference. The expression of the DeltaNp63 mRNA was significantly higher in low differentiated group than in well and moderate differentiated group, without significant difference in age, gender, lymph node metastasis and clinical stage. Only 1 of 38 cases of esophageal squamous cell carcinoma tissues presented TAp63 mRNA expression and all esophageal normal tissues had no TAp63 mRNA expression. The positive rates of MDM-2 protein in esophageal squamous cell carcinoma tissues and normal tissues were 65.79% and 5% respectively, with significant difference. The expression level of the MDM-2 protein was higher significantly in low differentiated group than in well and moderate differentiated group, with significant difference in clinical stage and without significant difference in age, gender and lymph node metastasis. The DeltaNp63 mRNA expression in the esophageal squamous eel/carcinoma tissues was positively related to MDM-2 protein expression. Conclusion The major isotype expressed in the esophageal cancer and epithelia is DeltaNp63, which may play an important role in the carcinogenesis, development and prognosis of the esophageal squamous cell eareinoma. TAp63 is not the major isotype expressed in the esophageal cancer and epithelia, and not related to the carcinogenesis of esophageal squaraous cell carcinoma. High expression of MDM-2 protein is associated with the carcinogenesis of esophageal squamous cell cancer and related to the prognosis of esophageal squamous cell carcinoma. DeltaNp63 regulates the cell cycle and apoptosis through the pathway of MDM -2 and causes the carcinogenesis of esophageal squamous cell cancer.