Urea transport B gene induces melanoma B16 cell death via activation of p53 and mitochondrial apoptosis.

Abstract

Urea Transporter B (UT‐B) is a membrane channel protein that mediates the rapid transmembrane transport of urea and participates in urine concentration. Urea Transporter B is expressed in skin, but we found that there is little expression in human melanoma tissue. In this study, we examined the effects of UT‐B overexpression in melanoma. The results indicated that there is no UT‐B mRNA expression in B16 cells, and UT‐B overexpression repressed B16 cell proliferation and induced apoptosis in vitro. We show that UT‐B overexpression causes increased reactive oxygen species production, which may be caused by mitochondria dysfunction. The mitochondrial membrane potential (ΨΔm) was lower in UT‐B‐overexpressing B16 cells. The proteins involved in complexes I, III, IV and V of the respiratory chain were clearly downregulated in UT‐B‐overexpressing B16 cells, which would strongly reduce the activity of the electron transport chain. We found that mitochondrial release of cytochrome C into the cytoplasm also increased, indicating that apoptosis had been activated. In addition, UT‐B overexpression reduced AKT phosphorylation and MDM2 expression and increased p53 expression; p53 activation may be involved in the anticancer effects of UT‐B overexpression. Urea Transporter B overexpression also inhibited tumor growth in vivo. In conclusion, we demonstrated that UT‐B may be related to the occurrence of melanoma and play a role in tumor development.