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


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.


CONCLUSIONS
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.
Blomberg Jensen
Martin
M
Department of Growth and Reproduction, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark. mabj@rh.regionh.dk
Andersen
Claus Bøgelund
CB
Nielsen
John E
JE
Bagi
Per
P
Jørgensen
Anne
A
Juul
Anders
A
Leffers
Henrik
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D014807:Vitamin D / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; C406322:vitamin D 1-alpha hydroxylase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase