Recombinant expression of different mutant K-ras gene in pancreatic cancer Bxpc-3 cells and its effects on chemotherapy sensitivity
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- 作者：TengFei Shao (1)
YuanTing Zheng (1)
Bei Zhao (1)
Tao Li (1)
KeGuang Cheng (2)
WeiMin Cai (1) - 关键词：cancer chemotherapeutic ; anti ; cancer drug ; K ; ras ; mutation ; plasmids ; pancreas
- 刊名：Science China Life Sciences
- 出版年：2014
- 出版时间：October 2014
- 年：2014
- 卷：57
- 期：10
- 页码：1011-1017
- 全文大小：1,577 KB
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YuanTing Zheng (1)
Bei Zhao (1)
Tao Li (1)
KeGuang Cheng (2)
WeiMin Cai (1)
1. Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, 201203, China
2. Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Education of China, School of Chemistry & Chemical Engineering, Guangxi Normal University, Guilin, 541004, China - ISSN：1869-1889
文摘
K-ras is a member of ras gene family which is involved in cell survival, proliferation and differentiation. When a mutation occurs in ras gene, the activation of Ras proteins may be prolonged to induce oncogenesis. However, the relationship between K-ras mutation and clinical outcomes in pancreatic cancer patients treated with chemotherapy agents is still under debate. In this study, we constructed five pAcGFP1-C3 plasmids for different types of K-ras gene (WT, G12V, G12R, G12D, and G13D) and stably transfected human pancreatic cancer Bxpc-3 cells with these genes. The wild type and mutant clones showed a comparable growth and expression of K-Ras-GFP fusion protein. The expression of some K-ras mutations resulted in a reduced sensitivity to gefitinib, 5-FU, docetaxel and gemcitabine, while showed no effects on erlotinib or cisplatin. Moreover, compared with the wild type clone, K-Ras downstream signals (phospho-Akt and/or phospho-Erk) were increased in K-ras mutant clones. Interestingly, different types of K-ras mutation had non-identical K-Ras downstream signal activities and drug responses. Our results are the first to reveal the relationship between different K-ras mutation and drug sensitivities of these anti-cancer drugs in pancreatic cancer cells in vitro.