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

<p>Abstract</p> <p>Background</p> <p>Pancreatic 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...

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Main Authors: Cui Ping, Liu Jianguo, Yip-Schneider Michele, Myer David, Dong Zizheng, Li Zhaomin, Schmidt C Max, Zhang Jian-Ting
Format: Article
Language:English
Published: BMC 2010-11-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/10/598
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author Cui Ping
Liu Jianguo
Yip-Schneider Michele
Myer David
Dong Zizheng
Li Zhaomin
Schmidt C Max
Zhang Jian-Ting
author_facet Cui Ping
Liu Jianguo
Yip-Schneider Michele
Myer David
Dong Zizheng
Li Zhaomin
Schmidt C Max
Zhang Jian-Ting
author_sort Cui Ping
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Pancreatic 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.</p> <p>Methods</p> <p>Western 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.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>The 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.</p>
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spelling doaj.art-8fb8612eb36447aa8c3b98b4689114e32022-12-22T03:29:30ZengBMCBMC Cancer1471-24072010-11-0110159810.1186/1471-2407-10-598Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancersCui PingLiu JianguoYip-Schneider MicheleMyer DavidDong ZizhengLi ZhaominSchmidt C MaxZhang Jian-Ting<p>Abstract</p> <p>Background</p> <p>Pancreatic 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.</p> <p>Methods</p> <p>Western 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.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>The 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.</p>http://www.biomedcentral.com/1471-2407/10/598
spellingShingle Cui Ping
Liu Jianguo
Yip-Schneider Michele
Myer David
Dong Zizheng
Li Zhaomin
Schmidt C Max
Zhang Jian-Ting
Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
BMC Cancer
title Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
title_full Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
title_fullStr Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
title_full_unstemmed Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
title_short Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
title_sort role of 14 3 3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
url http://www.biomedcentral.com/1471-2407/10/598
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