Study of betatrophin effects on Wnt signaling pathway

Wnt signaling has fundamental roles in survival, cell proliferation, cell fate and any disorder in it, may lead to numerous malignancies including HepatoCellular Carcinoma (HCC). Nearly 95% of diagnosed HCC cases, showed aberrance in the Wnt signaling pathway. Two key genes in this pathway are WIF1 and β-catenin, the subnormal function of them can cause the activation of the Wnt pathway and subsequently, cell proliferation and carcinogenesis occur. So any substance which can inhibit this pathway is considered valuable. Betatrophin is a newly identified protein which is upregulated in HCC. In this study, we investigated the effect of this protein on the expression level of WIF1 and β catenin. Recombinant betatrophin was produced in the BL21 system and the purification of it was performed by Ni-NTA chromatography. After treatment of HepG2 cell lines with different concentrations of betatrophin, total cell RNA was extracted and Real-Time PCR was conducted in order to analyze the mRNA levels of WIF-1 and β-catenin. Betatrophin could increase the expression of WIF-1 up to 1.6 fold and decrease the expression of β-catenin by up to 0.4 fold. WIF-1 is the antagonist of Wnt proteins and it can inhibit the Wnt pathway, down-regulation of it has been shown in many malignancies and at the other hand accumulation of β-catenin as well, has been observed in tumors. So these results suggest that betatrophin by increasing and decreasing of WIF1 and β catenin respectively is capable to inhibit the Wnt signaling pathway and it can be used as an anti-cancer drug.

کلیدواژه ها:

Wnt signaling pathway ، Betatrophin ، WIF-1 ، β-catenin ، Carcinogenesis