Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
Open Access
- 1 November 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 10 (1), 598
- https://doi.org/10.1186/1471-2407-10-598
Abstract
Background 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. Methods 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. Results 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. Conclusion 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.Keywords
This publication has 44 references indexed in Scilit:
- 14-3-3σ Modulates Pancreatic Cancer Cell Survival and InvasivenessClinical Cancer Research, 2008
- Identification of Novel Nasopharyngeal Carcinoma Biomarkers by Laser Capture Microdissection and Proteomic AnalysisClinical Cancer Research, 2008
- Oligomerization Domain of the Multidrug Resistance–Associated Transporter ABCG2 and Its Dominant Inhibitory ActivityCancer Research, 2007
- 14-3-3σ Methylation in Pretreatment Serum Circulating DNA of Cisplatin-Plus-Gemcitabine-Treated Advanced Non–Small-Cell Lung Cancer Patients Predicts Survival: The Spanish Lung Cancer GroupJournal of Clinical Oncology, 2005
- Mcl-1, Vascular Endothelial Growth Factor-R2, and 14-3-3σ Expression Might Predict Primary Response against Radiotherapy and Chemotherapy in Patients with Locally Advanced Squamous Cell Carcinomas of the Head and NeckClinical Cancer Research, 2005
- 14-3-3σ Expression Is an Independent Prognostic Parameter for Poor Survival in Colorectal Carcinoma PatientsClinical Cancer Research, 2005
- Distribution and significance of 14‐3‐3σ, a novel myoepithelial marker, in normal, benign, and malignant breast tissueThe Journal of Pathology, 2004
- Decreased expression of 14-3-3σ in neuroendocrine tumors is independent of origin and malignant potentialOncogene, 2002
- The G2/M Regulator 14-3-3ς Prevents Apoptosis through Sequestration of BaxJournal of Biological Chemistry, 2001
- 14‐3‐3 proteins: key regulators of cell division, signalling and apoptosisBioEssays, 2001