Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers

BMC Cancer

Research Article

Zhaomin Li¹  Jianguo Liu¹  David Myer¹  Ping Cui¹  Zizheng Dong¹  Jian-Ting Zhang²  C Max Schmidt³  Michele Yip-Schneider⁴ 

[1] Department of Pharmacology and Toxicology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Pharmacology and Toxicology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;IU Simon Cancer Center, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Surgery, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;IU Simon Cancer Center, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Surgery, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;IU Simon Cancer Center, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;

关键词: Pancreatic Cancer;    Gemcitabine;    Pancreatic Cancer Cell;    Mitoxantrone;    Human Pancreatic Cancer;   

DOI  :  10.1186/1471-2407-10-598

 received in 2010-06-22, accepted in 2010-11-01,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis.MethodsWestern blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays.ResultsWe found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest.ConclusionThe increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients.

【 授权许可】

Unknown   
© Li et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.