Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20132
標題: MEK/ERK訊號調控GCIP在肺腺癌轉移機制之功能探討
MEK/ERK pathway-mediated GCIP expression involved in metastases of lung adenocarcinoma.
作者: 林冠廷
Lin, Kuan-Ting
關鍵字: lung adenocarcinoma
肺癌
metastasis
ERK
轉移
ERK
出版社: 生物醫學研究所
引用: Bogenrieder T, Herlyn M (2003). Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22: 6524-36. Chang MS, Chang CL, Huang CJ, Yang YC (2000). p29, a novel GCIP-interacting protein, localizes in the nucleus. Biochem Biophys Res Commun 279: 732-7. Chen JJ, Peck K, Hong TM, Yang SC, Sher YP, Shih JY et al (2001). Global analysis of gene expression in invasion by a lung cancer model. Cancer Res 61: 5223-30. Chen WC, Su PF, Jin YT, Chang MC, Chang TW (2008). Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease-free survival, mucinous differentiation and response to chemotherapy. Histopathology 53: 554-60. Chu YW, Yang PC, Yang SC, Shyu YC, Hendrix MJ, Wu R et al (1997). Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 17: 353-60. Friedl P, Gilmour D (2009). Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 10: 445-57. Lin YW, Chuang SM, Yang JL (2003). Persistent activation of ERK1/2 by lead acetate increases nucleotide excision repair synthesis and confers anti-cytotoxicity and anti-mutagenicity. Carcinogenesis 24: 53-61. Ma W, Stafford LJ, Li D, Luo J, Li X, Ning G et al (2007). GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. J Cell Biochem 100: 1376-86. Ma W, Xia X, Stafford LJ, Yu C, Wang F, LeSage G et al (2006). Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis. Oncogene 25: 4207-16. Natrajan R, Louhelainen J, Williams S, Laye J, Knowles MA (2003). High-resolution deletion mapping of 15q13.2-q21.1 in transitional cell carcinoma of the bladder. Cancer Res 63: 7657-62. Sonnenberg-Riethmacher E, Wustefeld T, Miehe M, Trautwein C, Riethmacher D (2007). Maid (GCIP) is involved in cell cycle control of hepatocytes. Hepatology 45: 404-11. Takami T, Terai S, Yokoyama Y, Tanimoto H, Tajima K, Uchida K et al (2005). Human homologue of maid is a useful marker protein in hepatocarcinogenesis. Gastroenterology 128: 1369-80. Terai S, Aoki H, Ashida K, Thorgeirsson SS (2000). Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression. Hepatology 32: 357-66. Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S et al (2000). GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity. J Biol Chem 275: 20942-8. Xiang H, Wang J, Mao Y, Liu M, Reddy VN, Li DW (2002). Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway. Oncogene 21: 3784-91. Yao Y, Doki Y, Jiang W, Imoto M, Venkatraj VS, Warburton D et al (2000). Cloning and characterization of DIP1, a novel protein that is related to the Id family of proteins. Exp Cell Res 257: 22-32.
摘要: GCIP (Grap2 and Cyclin D Interacting Protein) is identified in yeast two hybrid screening using the Grap2 and Cyclin D1 as baits. Previously studies have shown that overexpression of GCIP reduced phosphorylation of RB and inhibited E2F1-mediated transcriptional activity. In colon cancer and breast cancer cell lines, ectopic expression of GCIP resulted in a significant inhibition on anchorage- independent growth. Further examination of GCIP protein level in tumors indicated that GCIP scores of breast carcinomas were significantly correlated with tumor histological grade and clinical outcome. In this study we investigated the expression and the biological function of GCIP in human lung adenocarcinoma cells. Our data showed that GCIP expression in CL1-5 cells, which exhibit a relative higher invasive ability as compared with its parental cells CL1-0, was significant lower than that in CL1-0 cells. Interestingly, the level of phosphorylated ERK in CL1-5 was higher than that in CL1-0 cells. U0126 treatment resulted in the increase of GCIP protein expression but not mRNA level in CL1-5 cells. Furthermore, the protein stability of GCIP in CL1-5 was also lower than that in CL1-0. It's likely that the lower protein stability of GCIP may result in the lower level of GCIP in CL1-5. To gain better understanding of the GCIP function in human lung adenocarcinoma, overexpression of GCIP reduced the invasive ability in CL1-5 cells. In contrast, knockdown of GCIP expression by siRNA in poorly invasive CL1-0 cell line enhanced its invasive ability. Taken together, these results indicate that GCIP play a critical role in anti-invasiveness and MEK/ERK signal pathway may control GCIP expression in human lung adenocarcinoma.
URI: http://hdl.handle.net/11455/20132
其他識別: U0005-2407200916292400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2407200916292400
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