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Recombinant expression of different mutant K-rasgene in pancreatic cancer Bxpc-3 cells and its effects on chemotherapy sensitivity
- Source :
- SCIENCE CHINA Life Sciences; October 2014, Vol. 57 Issue: 10 p1011-1017, 7p
- Publication Year :
- 2014
-
Abstract
- K-rasis a member of rasgene family which is involved in cell survival, proliferation and differentiation. When a mutation occurs in rasgene, the activation of Ras proteins may be prolonged to induce oncogenesis. However, the relationship between K-rasmutation 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-rasgene (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-rasmutations 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-rasmutant clones. Interestingly, different types of K-rasmutation had non-identical K-Ras downstream signal activities and drug responses. Our results are the first to reveal the relationship between different K-rasmutation and drug sensitivities of these anti-cancer drugs in pancreatic cancer cells in vitro.
Details
- Language :
- English
- ISSN :
- 16747305 and 18691889
- Volume :
- 57
- Issue :
- 10
- Database :
- Supplemental Index
- Journal :
- SCIENCE CHINA Life Sciences
- Publication Type :
- Periodical
- Accession number :
- ejs33807024
- Full Text :
- https://doi.org/10.1007/s11427-014-4724-0