Department of General Surgery, Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, China.
Acta Oncol. 2012 Jul;51(6):790-6. doi: 10.3109/0284186X.2012.665611. Epub 2012 Feb 27.
Cyclin-dependent kinase-like1 (CDKL1) is known as a new member of cyclin-dependent kinases. Whether genetic alterations of CDKL1 gene are involved in the development and/or progression of gastric cancer is still unknown.
Here, the expression of CDKL1 protein in paired specimens of gastric cancer tissues and corresponding normal gastric tissue (n = 66) was assessed by immunohistochemistry assay. We then used lentivirus-mediated knock down to specifically inhibit CDKL1 expression in human gastric cancer cell lines. Cell proliferation potential in vitro was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry.
We show for the first time that high expression of CDKL1 protein was observed in gastric cancer tissues compared with matched adjacent tissues. Loss of CDKL1 function in both SGC7901 and MGC-803 gastric cancer cells significantly decreases cellular proliferation and increases apoptosis (p < 0.01). Furthermore, we show that the reduction of CDKL1 with its siRNA stimulates the activation of Bcl-2-interacting killer (Bik) pro-apoptotic protein and attenuated the expression of proliferating cell nuclear antigen PCNA.
In summary, our data suggest that CDKL1 plays an important regulatory role in gastric cancer cell proliferation and survival, and therefore, may represent a new target for therapeutic intervention.
周期素依赖性激酶样 1（CDKL1）是周期素依赖性激酶家族的新成员。CDKL1 基因的遗传改变是否参与胃癌的发生和/或进展尚不清楚。
本研究通过免疫组织化学法检测了 66 对胃癌组织及其相应正常胃组织中 CDKL1 蛋白的表达。然后，我们使用慢病毒介导的敲低特异性抑制人胃癌细胞系中 CDKL1 的表达。体外细胞增殖潜能通过 MTT 和集落形成实验测定。细胞凋亡通过流式细胞术评估。
我们首次发现，与配对的相邻组织相比，胃癌组织中 CDKL1 蛋白表达较高。SGC7901 和 MGC-803 胃癌细胞中 CDKL1 功能丧失显著降低细胞增殖并增加细胞凋亡（p < 0.01）。此外，我们发现，用其 siRNA 降低 CDKL1 水平可刺激 Bcl-2 相互作用杀伤（Bik）促凋亡蛋白的激活，并减弱增殖细胞核抗原 PCNA 的表达。
综上所述，我们的数据表明 CDKL1 在胃癌细胞增殖和存活中发挥重要调节作用，因此，可能成为治疗干预的新靶点。
