癌基因Pim-1在涎腺腺样囊性癌中对线粒体-细胞凋亡通路的抑制作用研究

癌基因Pim-1在肿瘤中的重要作用与细胞凋亡密切相关,同时Pim-1还可导致RUNX3蛋白的异位表达。我们已证明RUNX3蛋白在细胞质中的异位表达和降解与涎腺腺样囊性癌（ACC）的发生、转移及预后密切相关，但Pim-1在ACC中的作用鲜有报道。本研究运用siRNA干扰、质粒转染、Westernblot、荧光发光、real-time PCR、流式细胞分析、免疫组化等技术，研究Pim-1在ACC的作用机制，包括：1) Pim-1在ACC中的基因功能，和Pim-1对RUNX3的调控以及对线粒体-细胞凋亡的抑制作用；2) 在临床ACC组织中研究Pim-1与RUNX3表达及细胞定位的关系，与线粒体-细胞凋亡中各关键分子的关系，以及与各临床参数的关系，同时进行预后分析。本研究将揭示Pim-1与ACC发生发展的关系，为评价Pim-1作为一个有效的肿瘤标志物用于ACC的诊断、治疗以及预后的可能性提供依据。

As an oncogene, Pim-1 belongs to the Ser/Thr kinase family, and the overexpression of Pim-1 is involved in the apoptosis suppression. It has been reported that Pim-1 kinase phosphorylates RUNX3 and alters its subcellular localization.As a tumor supressor gene, RUNX3 can induce the mitochondrial-depended apoptosis. RUNX3 mislocalization is involved in the apoptosis. Our previous study showed that the RUNX3 mislocalization was related to the progression of the salivary gland adenoid cystic carcinoma (ACC). However, there is no report concerns about the Pim-1 and the ACC development. This study is supposed: 1. to investigate the alteration of the RUNX3 expression and cellular location as well as the apoptosis-related factors in the ACC cell lines after Pim-1 siRNA, to clarify whether the apoptosis is depended on the mitochondrial pathway; 2. to validate the gene function of Pim-1 on the ACC and hOMF cell line; 3. to detect the relationship between the Pim-1 and RUNX3, the Pim-1 and the apoptosis-related factors, the Pim-1 and the clinical pathologic and prognois parameters in the clinical ACC tissue. This study will demonstrate the anti-apoptotic function of Pim-1 in the ACC progression. It can insight into the ACC diagnosis, therapy and prognosis by targeting the Pim-1.