Abstract | BACKGROUND: 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.
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Authors | Zhaomin Li, Zizheng Dong, David Myer, Michele Yip-Schneider, Jianguo Liu, Ping Cui, C Max Schmidt, Jian-Ting Zhang |
Journal | BMC cancer
(BMC Cancer)
Vol. 10
Pg. 598
(Nov 01 2010)
ISSN: 1471-2407 [Electronic] England |
PMID | 21040574
(Publication Type: Journal Article)
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Chemical References |
- 14-3-3 Proteins
- Antineoplastic Agents
- Biomarkers, Tumor
- Exonucleases
- Exoribonucleases
- SFN protein, human
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Topics |
- 14-3-3 Proteins
(physiology)
- Antineoplastic Agents
(pharmacology)
- Biomarkers, Tumor
(physiology)
- Cell Cycle
- Cell Line, Tumor
- DNA Damage
- Drug Resistance, Neoplasm
- Exonucleases
(physiology)
- Exoribonucleases
- Gamma Rays
- Gene Expression Regulation, Neoplastic
- Humans
- Lymphatic Metastasis
- Pancreas
(metabolism)
- Pancreatic Neoplasms
(drug therapy, metabolism, radiotherapy)
- Prognosis
- Treatment Outcome
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