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评估乳腺癌组织中细胞周期蛋白依赖性激酶样 1 的表达及其对癌细胞生长的调控。

Evaluation of cyclin-dependent kinase-like 1 expression in breast cancer tissues and its regulation in cancer cell growth.

机构信息

Department of Clinical Laboratory, Nanjing Medical University Cancer Hospital, Nanjing, PR China.

出版信息

Cancer Biother Radiopharm. 2012 Aug;27(6):392-8. doi: 10.1089/cbr.2012.1198.

Abstract

Cyclin-dependent kinase-like 1 (CDKL1) is a member of cell division control protein 2 (CDC2)-related serine-threonine protein kinase family, and it is likely to occur in malignant tumors, plays an important impact on the progress. This study aimed to evaluate the expression of CDKL1 in breast cancer and regulation in cancer cell growth. In the work, the CDKL1 mRNA level in fresh biopsy tissues from 186 breast cancer patients, with 98 benign tissues as negative control, and CDKL1 protein in 30 paraffin-embedded tissues from primary breast cancer patients were detected by the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay and immunohistochemical staining, respectively. The roles of CDKL1 in cell growth were analyzed with CDKL1 short hairpin RNA (shRNA) inhibitor-transfected cells. CDKL1 was overexpressed in breast cancer patients and had a positive detection efficiency of 77% (144/186), which showed statistically significant difference compared with estrogen receptor (ER), progesterone receptor (PR), P53, vascular endothelial growth factor (VEGF), and E-cadherin (E-cad) (p<0.05). Inhibiting CDKL1 function with shRNA, MCF-7 cells exhibited obvious accumulation at the G2/M phase and increased sensitivity to cell cycle chemotherapeutic drugs. The results suggested that the CDKL1 gene could be a potential tumor marker for diagnosis and a gene target for therapy.

摘要

细胞分裂周期蛋白依赖性激酶样 1(CDKL1)是细胞分裂控制蛋白 2(CDC2)相关丝氨酸/苏氨酸蛋白激酶家族的成员,可能发生在恶性肿瘤中,对进展起着重要影响。本研究旨在评估 CDKL1 在乳腺癌中的表达及其对癌细胞生长的调控作用。在这项工作中,通过实时逆转录聚合酶链反应(RT-PCR)检测了 186 例乳腺癌患者新鲜活检组织中的 CDKL1mRNA 水平,其中 98 例良性组织为阴性对照,并通过免疫组织化学染色检测了 30 例原发性乳腺癌患者石蜡包埋组织中的 CDKL1 蛋白。用 CDKL1 短发夹 RNA(shRNA)抑制剂转染的细胞分析了 CDKL1 在细胞生长中的作用。CDKL1 在乳腺癌患者中过度表达,阳性检出率为 77%(144/186),与雌激素受体(ER)、孕激素受体(PR)、P53、血管内皮生长因子(VEGF)和 E-钙黏蛋白(E-cad)相比具有统计学显著性差异(p<0.05)。用 shRNA 抑制 CDKL1 功能后,MCF-7 细胞在 G2/M 期明显积聚,并增加了对细胞周期化疗药物的敏感性。结果表明,CDKL1 基因可能是诊断的潜在肿瘤标志物和治疗的基因靶点。

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