Kang Min Ah, Kim Jong-Tae, Kim Joo Heon, Kim Soo-Young, Kim Young Ho, Yeom Young Il, Lee Younghee, Lee Hee Gu
Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
J Cancer Res Clin Oncol. 2009 Jun;135(6):761-9. doi: 10.1007/s00432-008-0510-3. Epub 2008 Nov 26.
CKS2 was identified as an upregulated gene in gastric cancer via our DNA microarray. This study was to verify the upregulation of CKS2 in many gastric cancer patients and to examine the CKS2-mediated cellular response.
CKS2 upregulation was analyzed using reverse transcriptase PCR, real-time PCR, and immunohistochemical and clinicopathological analyses. GFP-CKS2 or CKS2-siRNA was used to analyze the cellular localization and proliferation.
The strong upregulation of mRNA and protein levels of CKS2 was identified. In CKS2-overexpressing cells, tumor suppressor p53 and p21(cip1) were downregulated and cell growth was increased. In contrast, CKS2-siRNA-transfected cells showed an increased tumor suppressor expression and decreased cell growth.
We showed that CKS2 was significantly upregulated in gastric cancers and a high level of CKS2 was highly correlated with histologic tumor differentiation and pathological grade of the tumor size, lymph node, and metastasis stage. We suggest that the cell cycle regulator CKS2 might be deeply involved in gastric cancer progression.
通过我们的DNA微阵列分析，CKS2被鉴定为胃癌中上调的基因。本研究旨在验证CKS2在众多胃癌患者中的上调情况，并检测CKS2介导的细胞反应。
采用逆转录PCR、实时PCR、免疫组织化学和临床病理分析等方法分析CKS2的上调情况。利用绿色荧光蛋白标记的CKS2（GFP-CKS2）或CKS2小干扰RNA（CKS2-siRNA）分析细胞定位和增殖情况。
鉴定出CKS2的mRNA和蛋白水平强烈上调。在CKS2过表达的细胞中，肿瘤抑制因子p53和p21（cip1）下调，细胞生长增加。相反，转染CKS2-siRNA的细胞显示肿瘤抑制因子表达增加，细胞生长减少。
我们发现CKS2在胃癌中显著上调，且高水平的CKS2与肿瘤的组织学分化、肿瘤大小、淋巴结及转移阶段的病理分级高度相关。我们认为细胞周期调节因子CKS2可能在胃癌进展中起重要作用。
