非小细胞肺癌组织中蛋白激酶CK2的表达及其意义

Expression of protein kinase CK2 subunits in non-small-cell lung cancer tissues and its significance

目的:酪蛋白激酶Ⅱ(casein kinase Ⅱ,CK Ⅱ)也被称为蛋白激酶CK2。本研究探讨了蛋白激酶CK2的蛋白和基因的表达以及活性与非小细胞肺癌(non-small-cell lung carcinoma,NSCLC)临床病理之间的关系。方法:应用免疫组织化学SP法检测35例石蜡包埋的NSCLC组织及其癌旁"正常"组织和7例非肿瘤性肺组织标本中CK2催化亚基α、α’和调节亚基β蛋白的表达。应用RT-PCR检测10例新鲜肺癌灶组织及其癌旁"正常"组织和4例非肿瘤性肺组织标本中CK2各亚基mRNA的表达。应用同位素参入法测定细胞内CK2的活性。结果:免疫组织化学检测结果显示,CK2α和β亚基在NSCLC组织中的阳性率分别为62.9%和57.1%,高于癌旁"正常"组织的11.4%和25.7%(P<0.05),也高于非肿瘤性肺组织的28.6%和42.9%,但P>0.05。CK2α’亚基在NSCLC组织中的阳性率为65.7%,高于癌旁"正常"组织和非肿瘤性肺组织(42.9%和42.9%,但P>0.05);CK2各亚基的表达与患者的年龄、性别和肿瘤临床分期无关(P>0.05)。CK2α’的表达与细胞的分化程度和组织学分型无关;CK2α的表达与细胞的分化程度相关(r=0.388,P<0.05),与组织分型无关。低分化组的CK2α的表达高于中、高分化组(P<0.05)。CK2β在肺鳞癌中的表达高于腺癌(P<0.05),且与细胞的分化程度无关。在NSCLC组织中,无论是CK2α还是CK2α’,均与CK2β的表达呈正相关(r=0.439,P<0.05;r=0.45,P<0.05)。CK2各亚基mRNA的表达水平均高于其癌旁"正常"组织和非肿瘤良性病变组织。肺癌组织CK2的活性约为其癌旁"正常"组织的5.4倍,是非肿瘤良性病变组织的3.6倍。结论:蛋白激酶CK2在NSCLC组织中有较高表达,其高表达与NSCLC的发生和发展有关。与CK2α’亚基相比,CK2α或β亚基可能是更为理想的生物学标志物。

Objective：Casein kinase II is also called protein kinase CK2. This study was to explore the mRNA expression and enzyme activity of CK2 alpha, alpha＇ and beta subunits in the tissues of non-small cell lung cancer （NSCLC） , and investigate their correlations with clinicopathologic features of NSCLC. Methods： Immunohistochemical method （SP） was used to examine the expression of CK2 alpha, alpha＇ and beta subunits in paraffin-embedded speciments of 7 benign lesions, 35 primary lung carcinomas and matched pericancerous tissues. The mRNA expressions of CK2 subunits were evaluated by reverse transcription-polymerase chain reaction （RT-PCR） in 4 benign lesions, 10 primary lung carcinomas and matched peritumor tissues and the activity of CK2 was measured by using isotope incorporation assay. Results：The positive rates of CK2 alpha and beta subunits （62.9% and 57.1% ） were significantly higher in NSCLC tissues than those in matched adjacent noncancerous tissues （ 11.4% and 25.7%, P 〈 0.05 ） and benign lesions tissues （28.6% and 42.9% , P 〉0.05）. The positive rate of CK2 alpha＇ subunit （65.7%） was higher in NSCLC tissues than that in matched adjacent noncancerous tissues and benign lesions tissues （42.9% and 42.9% , P 〉 0.05 ）. The expression levels of CK2 subunits had no correlation with gender, age, and pathologic stage （TNM） of the patients （P 〉 0.05 ）. The expression level of CK2 alpha＇ subunit was not related with cell differentiation and histological classification; the expression level of CK2 alpha subunit was associated with cell differentiation （ r =0. 388, P 〈 0.05 ） but not related with histological classification. The positive rate of CK,2 alpha subunit was significantly higher in poorly differentiated group than that in moderately differentiated and well-differentiated groups （ P 〈 0.05 ）. The positive rate of CK2 beta subunit was significantly higher in squamous cell carcinoma than that in adenocarcinoma （ P 〈 0.05 ） but it was not related with the degree of cell differentiation. The expression level of CK2 beta subunit positively correlated with that of CK2 alpha or alpha＇ subunit in NSCLC （ r = 0.439, P 〈 0.05 ; r = 0.45, P 〈 0.05 ）. The mRNA expression levels of the three CK2 subunits were higher in lung tumors compared with the corresponding pericancerous lung tissues and non-tumor benigh lesions tissues. The average activity of CK2 in the lung carcinomas was 5.4-fold higher than that in matched adjacent noncancerous tissues and 3.6-fold higher than that in benign lesion tissues. Conclusion：Protein kinase CK2 subunits are highly expressed in NSCLC and their overexpressiou have correlation with the tumorigenesis and development of NSCLC. As a biological marker, CK2 alpha or beta subunit may be better than CK2 alpha＇.