CKS1基因影响鼻咽癌细胞增殖和侵袭的机制研究

项目名称： CKS1基因影响鼻咽癌细胞增殖和侵袭的机制研究

项目编号： No.81201523

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 石磊

作者单位： 中南大学

项目金额： 24万元

中文摘要： 细胞周期蛋白激酶亚基1（CKS1）蛋白参与细胞周期的调控，促进细胞增殖，目前已发现CKS1基因在多种肿瘤中高表达，并且与多种肿瘤的癌变和进展相关，被认为是潜在的诊断和预后因子。我们发现在鼻咽癌肿瘤组织中也存在CKS1基因高表达，并且CKS1基因沉默引起MAPK细胞内信号转导通路失磷酸化，并引起细胞周期泛素化酶SKP2表达降低，导致鼻咽癌细胞凋亡和生长抑制。CKS1基因过表达的鼻咽癌细胞对化疗药物顺铂的杀细胞作用存在耐受。这些研究基础提示，CKS1基因可能影响鼻咽癌细胞的增殖和耐药，与鼻咽癌的癌变和发展相关。我们将在此研究基础上进一步探讨CKS1基因高表达与鼻咽癌不同临床分期的关系，研究CKS1在鼻咽癌中的作用，及其影响肿瘤细胞增殖和耐药的机制，为临床更好的治疗鼻咽癌提供新的思路。

中文关键词： cyclin-dependent protein kinas；放疗抵抗；淋巴结转移；鼻咽癌；p53/MDM2

英文摘要： Cdc28 protein kinase regulatory submit 1(CKS1) has been well documented its role in regulating cell cycle by ubiquting the cell cycle inhibitor P27.CKS1 has been found high expressed in multi-tumors and been presumed to be a potential factor in tumor diagnosis and prognosis. Our datas shown that high-expression of CKS1 was found in nasopharyngeal carcinoma(NPC). Knock-down of CKS1 in NPC cell line by si-RNA reduced to cell apoptosis and growth inhibition through inactivation of MAPK cell signaling pathway and low-expression of SKP2. Furthermore, we found that forced expression of CKS1 by lentivirus vector-mediated CKS1-DNA transfection in NPC cells increased drug-resistance. Under the base of our previous research, we would study the relationship between CKS1 expression and NPC in various clinical stages. The functional role and mechanisms of CKS1 in NPC would perstetured on which influence cell proliferation and survival. In this study, we aim to further demonstrate that CKS1 plays a crucial role in NPC cell growth and survival and provid more applications for cancer treatment.

英文关键词： cyclin-dependent protein kinase regulatory subunit；radio- resistance；lymph node metastasis (LNM)；Nasopharyngeal carcinoma (NPC)；p53/MDM2