TGF-β1 induces the expression of fascin1 in gastric cancer cells via SMAD-independent pathway
WANG Guohui;GU Yonghong;ZHU Shaihong;FU Hua;Centre of Experimental Medicine,the Third Xiangya Hospital of Central South University;Department of Pathology, the Third Xiangya Hospital of Central South University;
Objective To study the effect of transforming growth factor-β1(TGF-β1) on fascin1 expression and clarify the mechanism. Method Gastric cancer cell line MKN45 was used in the study, and the effect of TGF-β1(10 ng/ml)with various treatment time on fascin1 expression was detected by Western blot. The effect of SMAD-dependent pathway on TGF-β1-induced fascin1 expression was examined by transient transfection with SMAD2 and SMAD4 siRNA.The effect of SMAD-independent pathway on TGF-β1-induced fascin1 expression was tested using specific inhibitors of ERK, JNK and P38 pathways. Result TGF-β1(10 ng/ml) induced the expression of fascin1 in gastric cancer cell line MKN45 after 24 h and 48 h of treatment as compared with that before treatment(0 h), with statistically significant difference observed(P0.05). By transient transfection of SMAD siRNA by RT-PCR and western blot, the expression of SMAD2 and SMAD4 were suppressed, while HK was almost not affected by the gene expression of SMAD2 and SMAD4. After effective inhibition of SMAD2 and SMAD4 expression, the TGF-β1-induced fascin1 expression remained unchanged. While it was suppressed by the specific inhibitors of JNK and ERK pathways, SP600125 and PD98059 respectively, but not by inhibitors of P38, SB203580. Conclusion TGF-β1 regulates the expression of fascin1, by mediating ERK and JNK signaling pathways.
【CateGory Index】： R735.2