The crosstalk between Wnt and TGF-? signaling pathway in prostate cancer cell PC-3 / 中华泌尿外科杂志

ABSTRACT

Objective To investigate the crosstalk between Wnt signaling pathway and TGF-? signaling pathway in prostate cancer cell line PC-3. Methods Luciferase report assay and RT-PCR methods were used to explore the crosstalk between two pathways. Results Wnt signaling pathway activated TGF-? responsive CAGA-luciferase reporter activity. ?-catenin(WT), TCF-4(WT), GSK3? (KM) activated while TCF-4(DN) inhibited CAGA reporter activity. ?-catenin(WT), TCF-4(WT) synergized to activate TGF-? signaling while TCF-4(DN) had converse effect.TGF-? signaling pathway activated LEF-1 luciferase activity through a Smad3-dependent manner.Smad7 activated LEF-1 luciferase activity,Smad3 and Smad4 also synergically activated LEF-1 reporter activity.?-catenin(WT),TCF-4(WT) cooperated with each other to the activity of cyclinD1 promoter luciferase while Smad3 inhibited cyclinD1 promoter activity.The inhibitory effect of Smad3 on cyclinD1 promoter could be partially reversed by co-transfecting ?-catenin(WT),TCF-4(WT).TGF-? induced the expression of VEGF in PC-3 cells and this effect was enchanced by LiCl addition. Conclusions Wnt signaling pathway and TGF-? signaling pathway can activate each other in prostate cancer cell line PC-3.Two pathways have crosstalk and this might be important for the development and progression of prostate carcinoma.