Signal transducer and activator of transcription 3 (STAT3) is a recently characterized transcription factor which is essential to liver regeneration. We have previously reported that hepatic stimulator substance (HSS)...Signal transducer and activator of transcription 3 (STAT3) is a recently characterized transcription factor which is essential to liver regeneration. We have previously reported that hepatic stimulator substance (HSS), a novel growthpromoting substance, phosphorylated the epidermal growth factor (EGF) receptors and activated downstream RasMAP kinase (extracellular signal-regulated kinases, ERK1/2) cascade. However, whether HSS signal is related to STAT3pathway remains unclear. The present study is aiming to explore the regulatory effect of activation of ERK1/2 evoked by HSS on STAT3 phosphorylation and STAT3 signaling. Human hepatoma cell line HepG2 was stably transfected with HSS cDNA and HSS expression was measured by Northern blot. The results showed that the transfection of HSS into HepG2 resulted in remarkable increase in cellular proliferation as compared with the non-transfected cells, and it was further proved that the cellular proliferation in the HSS-transfected cells was related to ERK1/2 activation. Treatment of the cells with 50 μM of PD98059, an ERK1/2 specific upstream inhibitor, resulted in ERK1/2 inactivation completely.Inhibition of ERK1/2 allowed the tyrosine of STAT3 to be phosphorylated in a dose-dependent manner to PD98059.Furthermore, transient transfection of STAT3 mutant (STAT3S727A) into HSS-bearing cells could remarkably reverse the inhibitory effect of ERK1/2 on STAT3 phosphorylation. Based upon these results, it is concluded that ERK1/2negatively modulates STAT3 phosphorylation and this function is dependent on residual serine-727 (S727) of STAT3.展开更多
Objective： Numerous studies examining the relationship between human epidermal growth factor receptor 2 （HER-2） overexpression and survival in patients with colorectal cancer （CRC） have yielded controversial resu...Objective： Numerous studies examining the relationship between human epidermal growth factor receptor 2 （HER-2） overexpression and survival in patients with colorectal cancer （CRC） have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value. Methods： Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios （HRs） and their corresponding 95% confidence intervals （95% Cls） were pooled in terms of disease-specific or overall survival. Results Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival （HR=1.10, 95% CI： 0.77-1.44）. Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival （HR=0.89, 95% CI： 0.50-1.29; HR=0.90, 95% Ch 0.43-1.37, respectively）, Conclusions： Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.39870285,No.0070342).
文摘Signal transducer and activator of transcription 3 (STAT3) is a recently characterized transcription factor which is essential to liver regeneration. We have previously reported that hepatic stimulator substance (HSS), a novel growthpromoting substance, phosphorylated the epidermal growth factor (EGF) receptors and activated downstream RasMAP kinase (extracellular signal-regulated kinases, ERK1/2) cascade. However, whether HSS signal is related to STAT3pathway remains unclear. The present study is aiming to explore the regulatory effect of activation of ERK1/2 evoked by HSS on STAT3 phosphorylation and STAT3 signaling. Human hepatoma cell line HepG2 was stably transfected with HSS cDNA and HSS expression was measured by Northern blot. The results showed that the transfection of HSS into HepG2 resulted in remarkable increase in cellular proliferation as compared with the non-transfected cells, and it was further proved that the cellular proliferation in the HSS-transfected cells was related to ERK1/2 activation. Treatment of the cells with 50 μM of PD98059, an ERK1/2 specific upstream inhibitor, resulted in ERK1/2 inactivation completely.Inhibition of ERK1/2 allowed the tyrosine of STAT3 to be phosphorylated in a dose-dependent manner to PD98059.Furthermore, transient transfection of STAT3 mutant (STAT3S727A) into HSS-bearing cells could remarkably reverse the inhibitory effect of ERK1/2 on STAT3 phosphorylation. Based upon these results, it is concluded that ERK1/2negatively modulates STAT3 phosphorylation and this function is dependent on residual serine-727 (S727) of STAT3.
基金Project supported by the National Natural Science Foundation of China(Nos.81101837 and 81071959)the Research Fund for the Doctoral Program of Higher Education of China(No.20110101120129)
文摘Objective： Numerous studies examining the relationship between human epidermal growth factor receptor 2 （HER-2） overexpression and survival in patients with colorectal cancer （CRC） have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value. Methods： Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios （HRs） and their corresponding 95% confidence intervals （95% Cls） were pooled in terms of disease-specific or overall survival. Results Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival （HR=1.10, 95% CI： 0.77-1.44）. Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival （HR=0.89, 95% CI： 0.50-1.29; HR=0.90, 95% Ch 0.43-1.37, respectively）, Conclusions： Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.
