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標題: 14-3-3 zeta (YWHAZ)蛋白對於肺腺癌細胞 調控上皮塑性與轉移的重要性
The role of 14-3-3 zeta protein (YWHAZ) in regulating epithelial plasticity and lung adenocarcinoma cell metastasis
作者: 楊孟芳
Fang, Yang-Meng
關鍵字: 14-3-3 zeta protein;14-3-3zeta;lung adenocarcinoma;肺癌;轉移
出版社: 生物醫學研究所
肺癌,尤其是肺腺癌,是近年來具有高發生率和極高死亡率之惡性腫瘤,而癌轉移則是導致病患死亡的主因。癌轉移與細胞上皮塑性(epithelial plasticity)的改變有很大的關連。為找尋新的癌轉移相關基因,我們以競爭性基因體核酸雜交微陣列(CGHarray)分析不同侵襲與轉移能力肺癌細胞株之基因體中基因拷貝數的變異(CL1-0
Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the most common cause of cancer deaths worldwide, and metastasis is the major cause leading to mortality for cancer patients. The alteration of epithelial plasticity is crucial events during metastasis. To identify the novel metastasis-related genes, we used a method that simultaneously integrated microarray-based comparative genomic hybridization and affymetrix gene expression profiles to identifiy a potential candidate, 14-3-3zeta, in a lung cancer cell line model with different invasion capability (CL1-5 > CL1-0 cell line). 14-3-3zeta protein plays an important role in a wide variety of cellular processes, including signal transduction, cell cycle regulation and apoptosis. However, its role in lung cancer metastasis is unclear. This study will investigate the role of 14-3-3zeta protein in regulating epithelial plasticity and metastasis of lung adenocarcinoma cell. First, microarray data will be confirmed by real-time PCR and western blotting to demonstrate that the genomic copy number, mRNA and protein level of 14-3-3zeta in CL1-5 and CL1-0 lung caner cells. We also observe the distribution of 14-3-3zeta protein in subcellular localization. Second, we will overexpress or silence 14-3-3zeta in lung caner cells and estimate the ability of invasion, migration, as well as morphology. According to preliminary results, we presume that the protein may be involved in tumor metastasis via cytoskeleton rearrangement and regulating epithelial plasticity. To evaluate the alternation of epithelial plasticity, the amount of EMT marker,and G/F actin ratio will be performed by western blotting and immunofluorescence. In addition, we clarify the interaction molecule and modulating pathway of 14-3-3zeta protein. Furthermore, stable lung adenocarcinoma cell lines will be seeded onto immune-compromised (SCID) mice to suggest the influence of 14-3-3zeta protein. Consistent with an animal experiment, 14-3-3zeta is indeed essential for tumorigenesis and lung tumor metastasis. Finally, we check 14-3-3zeta expression in lung adenocarcinoma specimen with different stage, and analyze the survival and recurrent of 60 patients. These efforts may assist us to understand the role of 14-3-3zeta protein in human lung adenocarcinoma metastasis, and may offer some help in the treatment of lung cancer.
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