ZIP11 and ZnT1 are differentially expressed in human renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is a solid, malignant, and heterogeneous tumor originating in the renal tubular epithelium. There are several histopathological classifications, with clear-cell carcinoma (ccRCC) being the most common. Its occurrence is associated with mutations in the von Hippel-Lindau gene, which regulates cellular responses to stress, division, death, and differentiation. The loss of functionality affects the degradation of hypoxia-inducible factor (HIF). In turn, the HIF1α subunit becomes highly expressed. Zinc (Zn) is the second most abundant trace element in the human body, and small variations in its concentration can lead to disturbances in the cellular environment. Zn transporters play a fundamental role in Zn homeostasis. In this study, the expression and localization of the Zn channels ZIP11 and ZnT1 were verified in normal tubular renal cells (HK-2) and a clear cell renal adenocarcinoma line (786-0). RT-PCR and western blotting data showed that the ZIP-11 channel was highly expressed in tumor cells. In contrast, the ZnT1 channel was expressed at lower levels in tumor cells. Immunofluorescence data revealed different localization patterns between the two lines. The expression of ZIP-11 in HK-2 cells was predominantly cytoplasmic, while in 786-0 tumor cells, in addition to strong cytoplasmic staining, nuclear staining was also observed. ZnT1 expression in HK-2 cells was cytoplasmic and accentuated on the cell membrane, while that in 786-0 tumor cells was nuclear. These results demonstrated different expression patterns of the key Zn transporters, ZIP11 and ZnT1, in RCC cells compared to those in the normal kidney epithelium. Further elucidation of the molecular mechanisms underlying Zn dysregulation in RCC may reveal potential therapeutic targets.