Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

Abstract

Background: The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal the segmental location of expression, and clarify whether the reported loss of VDR in CCc is coincident with alterations of vitamin D metabolism.

Materials and methods: Tissue was obtained from nine patients (eight CCc and one atrophic kidney), mRNAs were detected with RT-PCR and in situ hybridisation (ISH), and expression of proteins determined by immunohistochemistry and western blotting.

Results: We detected expression of VDR and the vitamin D metabolising enzymes in normal kidney. VDR and CYP27B1 were strongly expressed in proximal tubules, while CYP2R1 and CYP27A1 had a marked expression in distal tubules. In CCc expression was lost for VDR and all the enzymes, except for very few cells expressing all the investigated proteins.

Conclusion: This study shows that VDR and all the vitamin D metabolising enzymes are expressed in the normal kidney. During the malignant transformation to CCc, expression of VDR and the metabolising enzymes is lost, however the implications of this loss are unknown.