细胞周期蛋白依赖性激酶11在乳腺癌组织中的表达及临床意义

Expression and clinical significance of cyclin - dependent kinase 11 in human breast cancer tissues

目的检测细胞周期蛋白依赖性激酶11（CDK11）在乳腺癌组织中的表达，探讨CDK11的表达在乳腺癌病情评估、预后判断中的临床意义。方法Westernblot方法检测BT-474、MCF-7、MDA-MB-231、MDA-MB-468乳腺癌细胞株及HBL-100永生化的正常乳腺细胞中CDK11的表达，应用细胞免疫荧光技术检测MCF-7和MDA—MB-468细胞中CDK11的表达及亚细胞定位。应用Westernblot方法检测18例乳腺癌组织标本及对应的癌旁组织标本中CDK11的表达。应用商品化的乳腺癌组织芯片，免疫组织化学技术检测组织芯片中每个组织中CDK11的表达，并分析CDK11的表达水平与肿瘤病理分级、TNM分期等临床病理特征及患者生存时间的关系，探讨CDK11的临床意义。结果CDK11在BT-474、MCF-7、MDA—MB-231和MDA．MB-468细胞中的相对表达强度分别为0．95±0．03、0．83±0．02、0．39±0．07和0．91±0．03，均明显高于永生化的正常乳腺细胞的0．07±0．01（P〈0．01）。细胞免疫荧光染色结果显示CDK11在MCF-7和MDA—MB-468细胞中的表达主要定位于细胞核，在细胞质中有少量表达。组织芯片检测结果显示，CDK11在乳腺癌组织中的表达水平显著高于对应的正常乳腺组织（3．56分比2．56分，P〈0．01），病理学分级Ⅲ级乳腺癌组织中CDK11的表达水平高于Ⅱ级乳腺癌组织（3．50分比2．59分，P〈0．05）。CDK11高表达（≥4分）的乳腺癌患者的生存时间小于CDK11低表达（≤3分）的患者（P〉0．05）。此外，TNMⅢ期乳腺癌组织中CDK11的表达水平高于TNM11期乳腺癌组织（3．25分比2．92分，P〉0．05），死亡患者乳腺癌组织中CDK11的表达水平高于存活患者（3．57分比2．97分，P〉0．05），但差异无统计学意义。结论CDK11在乳腺癌组织中高表达，并与乳腺癌患者的临床病理特征及预后相关。

Objective To determine the expression levels of cyclin - dependent kinase 11 （CDK11 ） in human breast cancer tissues and evaluate the clinical significance of CDK11 expression in clinicopathology assessment and prognosis estimation. Methods The expression levels of CDK11 in 4 hu- man breast cancer cell lines BT - 474, MCF - 7, MDA - MB - 231 and MDA - MB - 468 as well as in one immortalized human breast cell line HBL - 100 were determined by Western blotting. Immunofluorescence assay was employed to detect the expression and subcellular localization of CDK11 in MCF - 7 and MDA - MB-468 cells. Furthermore, CDKll expression was also determined by Western blotting in 18 pairs of breast tumor tissues and their adjacent normal breast tissues, in addition, CDK11 levels in breast tumor tis- sue microarray were determined by immunohistochemistry, and the correlation of CDK11 expression with clinicopathological characteristics and survival time of breast cancer patients was evaluated. Results The relative expression of CDK11 in BT - 474, MCF - 7, MDA - MB - 231 and MDA - MB - 468 was 0. 95 ± 0.03,0. 83 ±0.02, 0. 39 ±0.07 and 0.91 ±0.03, respectively, which was significantly higher than that in the normal breast cells HBL - 100, which was 0. 07 ±0. 01 （P 〈0. 01 ）. Immunohistochemistry showed that CDK11 mainly expressed in the nuclear of MCF - 7 and MDA - MB - 468 cells, with little expression the cytoplasm. Tissue microarray demonstrated that the expression of CDK11 was significantly higher in breast cancer than that in the corresponding nontumorous breast tissues （3.56 vs. 2. 56, P 〈 0. 01 ）. CDK11 expression was significantly higher in pathological grade III breast tumor tissues compared with that in pathological grade II tissues （ 3.50 vs. 2. 59, P 〈 0. 05 ）. More importantly, the survival time of CDK11 high- staining （≥4） patients was shorter than that in the CDKll low- staining （ ≤3 ） patients （P 〉 0. 05 ）. Additionally, CDK11 expression was higher in TNM stage III breast tumor tissues compared with that in TNM stage II tissues （ 3.25 vs. 2.92, P 〉 0. 05 ）, and the expression of CDKI 1 in nonsurviv- al breast cancer tissues was higher than that in survival breast cancer tissues （3.57 vs. 2. 97, P 〉 0. 05 ）, although the difference was not statistically significant. Conclusion CDK11 is highly expressed in human breast cancer tissues, and the expression levels of CDKI 1 are related to the clinical pathological characteristics and prognosis of patients.