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Objective To investigate the expressions of cancerous inhibitor of protein phosphatase2A (CIP2A),phosphatidylinositol 3-kinase(PI3K),and survivin in pancreatic carcinomas and their clinical significance.Methods The expressions of CIP2A,PI3K,and survivin proteins were tested by immunohistochemistry in 64 cases of pancreatic carcinomas and adjacent paracancerous tissues.Results The positive rate of CIP2A in pancreatic carcinomas was significantly higher than adjacent paracancerous tissues (70.3％ vs 5.6％,P ＜0.05).Significant difference was observed in the expression rate of PI3K between the patients with pancreatic carcinomas and paracancerous tissues (73.4％ vs 8.3％,P ＜0.05).Significant difference was also observed in the expression rate of survivin between the patients with pancreatic carcinomas and paracancerous tissues (75.0％ vs 2.8％,P ＜0.05).CIP2A,PI3K,and survivin were significantly differentially expressed in pancreatic carcinoma among different tumor differentiation,tumor node metastasis (TNM) stage,and neural invasion and lymph node metastasis (all P ＜ 0.05).Spearman correlation analysis showed significantly positive correlation between the expressions of CIP2A and the others (PI3K and survivin) (both P ＜0.05),and between the expressions of PI3K and surviving (P ＜0.05).Conclusions CIP2A was involved in the development of pancreatic carcinomas and might activate the PI3K/Akt/survivin pathway.Our data identified CIP2A as a critical oncoprotein involved in cell proliferation,invasion,and metastasis.It could serve as a therapeutic target for pancreatic carcinomas.
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Objective To investigate the expressions of phosphatidylinositol 3-kinase (PI3K), Akt and E-cadherin and their clinical significance in thyroid papillary carcinomas.Methods Expressions of PI3K, Akt, and E-cadherin were detected in 62 cases of thyroid papillary carcinomas,30 cases of thyroid goiter and 30 cases of normal thyroid by immunohistochemistry (EnVison),and simultaneously compared with age, sex, tumor size, clinical tumor node metastasis( TNM) stages, and lymph node metastasis in thy-roid papillary carcinomas.Results The expression rate of PI3K, Akt, and E-cadherin was 74.2%(46/62), 66.1%(41/62), 16.1%(10/62),respectively.Expressions of three proteins in thyroid papillary carcinomas were significantly different from those in thyroid goiter and normal thyroid tissues ( P <0.05). The lower positive rates of PI3K and Akt proteins were obtained in the group of stageⅠ~Ⅱthan that in the group of stageⅢ~Ⅳ(χ2 =4.976, P =0.026;χ2 =6.233, P =0.013).Higher positive rates of PI3K and Akt proteins were obtained in the group of lymph-node metastasis than that in group of non-lymph-node metastasis (χ2 =6.675, P =0.010;χ2 =7.511, P =0.006).Higher positive rate of E-cadherin protein was obtained in the group of stage Ⅰ~Ⅱ than that in the group of stage Ⅲ ~Ⅳ (χ2 =6.558, P =0.010 ) .Higher positive rate of E-cadherin proteins was obtained in the group of non-lymph-node metastasis than that in the group of lymph node metastasis(χ2 =5.678, P =0.017).There was significant positive correlation between expressions of PI3K and Akt through Spearman correlation analysis ( r =0.423, P <0.05).PI3K was negatively correlated with E-cadherin with Spearman correlation analysis ( r =-0.527, P <0.05).Akt was also negatively correlated with E-cadherin ( r =-0.417, P <0.05).Conclusions PI3K/Akt pathway might regulate thyroid papillary carcinoma cells proliferation, invasion and metastasis.
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Objective To observe the effect of PDK ( phosphoinositol -3-kinase, PI3K)/Akt-Nrf2 (Nuclear factor -E2 related factor) signal pathway on γ-glutamylcysteine synthetase (γ-GCS) in the bronchial epithelial cells of rats treated with cigarette smoke extract (CSE). Methods The bronchial epithelial cells were dealt with 10% concentration of CSE for different time and pretreated with PI3k inhibitor (LY294002). The expressions of Nrf2,p-Akt and γ-GCS proteins were examined by immunocytochemistry, flow cytometry, immunofluorescence and western blot. The expressions of γ-GCS mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Reduced glutathione(GSH) content and the lev-el of γ-CCS activi-ty were examined. Results GSH content in CSElh group was significantly decreased, but still higher in CSE3 and 6 groups compared to the control. Nrf2 protein mainly located in the cytoplasm. Nrf2 plasmosin mainly increased in the nucleus in control group, and Nrf2 nucleic protein significantly enhanced in CSE1, 3 and 6 groups. P-Akt protein was up-regulated at lh, reached its peak at 3h, declined slightly at 6h after exposure to CSE. The tendency of the percentage of p-Akt positive cells was as same as p-Akt protein. γ-GCS mRNA, protein and activity, gradually increased in CSE lh, CSE 3h,CSE 6h groups. Pretreated with LY294002, the expression of p-Akt protein was markedly decreases, while Nrf2 plasmosin expressed strongly, and γ-GCS mRNA, protein, activity and GSH content were significantly decreased compared to CSE3h group. Linear correlation analysis demonstrated that there were a positive correlation among Nrf2 and γ-GCS,γ-GCS activity, and among p-Akt and Nrf2,GSH,γ-GCS,γ-GCS activity. Conclusion P13K/Akt signal path might participate in Nrf2 nuclear translocation via regulating the expression of γ-GCS.