Characterization of KPNA2 interactome and its physiological function in non-small cell lung cancer
| Autor: | Hsiang Pu Feng, 馮香菩 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 The process of nucleocytoplasmic shuttling is mediated by karyopherins. Dysregulated expression of karyopherins may trigger oncogenesis through aberrant distribution of cancer-associated proteins. Importin subunit alpha-2 (KPNA2) is overexpressed in several human caners, including non-small cell lung cancer (NSCLC) and has been reported as an invasiveness-associated protein. Previously, we found that KPNA2 involved in cell migration and proliferation in NSCLC. Herein, we applied gene knockdown and subcellular fractionation to analyze whether Rac1, one of KPNA2 interaction proteins, involves in KPNA2-mediated cell tumorigenesis. We found that knockdown of KPNA2 attenuated the nuclear entry of Rac1 in Hela cell, but not CL1-0 lung adenocarcinoma cell. The current study is focus on the validation of two potential KPNA2 cargo proteins those might contribute to KPNA2-medicated cell tumorigenesis in NSCLC. To examine the oncogenic effects of KPNA2 in vivo, we selected CL1-0 adenocarcinoma cell that with low invasiveness as a parental cell to generate the KPNA2-expressing stable clone for xenograft mouse model. The in vitro migration ability of KPNA2-expressing stable clones indeed increased as compared to the control cells. Subcutaneously injection of KPNA2-expressing stable clones in nude mice was used to evaluate whether overexpressed KPNA2 could promote tomorigenesis and metastasis in vivo. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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