Study on PTPN2 interacting protein and its role in lung cancer

• Main Authors: Hsuan-Yu Chen, 陳宣余
• Other Authors: 陳健尉
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/02011450377452031217

碩士 === 國立中興大學 === 分子生物學研究所 === 96 === According to statistical data in 2006 of Department of Health, the lung cancer is the main reason of death about malignant tumor in Taiwan, especially, adenocarcinomas is the most common one. Cancer is often caused by gene mutation, including oncogenes and tumor suppressor genes. Protein modification, such as phosphorylation and dephosphorylation, plays an important role to regulate many cellular responses including growth, metabolism and differentiation by activating different proteins. The aim of this study is to find which proteins interacting with PTPN2 (protein tyrosine phosphatase non-receptor type 2) by yeast two hybrid assay. PTPN2, belongs to PTP (protein tyrosine phosphatase) superfamily, is a signal transduction protein and regulates protein tyrosine phosphorylation through signal transduction pathway. PTP controls a diverse array of cellular responses including growth, proliferation, differentiation, migration, metabolism and survival. In this study, we utilized yeast two hybrid assay, and identified eight PTPN2-interacting proteins from human liver cDNA library. Previous work showed that CD74 (major histocompatibility complex class II invariant chain) and PRDX6 (Peroxiredoxin 6) could promote cell proliferation. Therefore, CD74 and PRDX6 were demonstrated in this study, and they are indeed confirmed to interact with PTPN2 by using co-immunoprecipitation. Additionally, the cell functions were also assayed under PTPN2 over- expression in cell. By immunofluorescent staining, we found that PTPN2 located in endoplasmic reticulum (ER). Overexpression of PTPN2 could significantly promote lung cancer cell proliferation by MTT assay, anchorage-dependent growth and anchorage-independent growth and increase the expression of phospho-ERK. However, PTPN2 had no effect on invasive and migrative ability. Taken together, we speculated that PTPN2 might promote lung cancer cell proliferation through ERK phosphorylation, and it needed more efforts to study in the future. By means of this study we provided a putative mechanism of modulating lung cancer cell proliferation, which might benefit to the development of target therapy in the future.