Vitamin D hydroxylases CYP2R1, CYP27B1 and CYP24A1 in renal cell carcinoma.
BACKGROUND
There is increasing evidence that vitamin D metabolites influence carcinogenesis. Besides its role in mineral homoeostasis, calcitriol, the active metabolite of vitamin D (1,25(OH)2 D3 ), is known to possess antiproliferative, proapoptotic and immunomodulatory effects in cancer. Concerning the synthesis of vitamin D, the hydroxylases CYP2R1, CYP27B1 and CYP24A1 play a critical role, and the latter molecule determines the biological half-life of 1,25(OH)2 D3 , which is synthesized in the proximal renal tubules.


METHODS
The adjacency of these two biological processes prompted us to investigate the gene expression of CYP2R1, CYP27B1 and CYP24A1 in patients with ccRCC. Using RT-PCR, we retrospectively compared mRNA expression profiles from human ccRCC tumour samples with those derived from the corresponding adjacent healthy tissues (n = 30).


RESULTS
We observed that all three genes (CYP2R1, CYP27B1 and CYP24A1) were upregulated in tumours compared with normal tissue (P < 0·0001). Moreover, CYP24A1 displayed a significantly higher expression in tumours than CYP27B1 (P < 0·05) and CYP2R1 (P < 0·0001), whereas no differences in the expression of these genes were found in healthy renal tissue. Gene expression of CYP2R1, CYP27B1 and CYP24A did not differ between pathological classifications (TNM, grading, presence of metastasis).


CONCLUSIONS
We thus conclude that upregulated gene expression of the catabolizing CYP24A1 as well as the synthesizing CYP2R1 and CYP27B1 may lead to a misbalance of vitamin D metabolites in ccRCC and thus contributing to its pathogenesis.
Faculty of Medicine, Goethe University Hospital, Frankfurt am Main, Germany.
Anja
A
Urbschat
Patrick
P
Paulus
Quirine Freiin
QF
von Quernheim
Patrick
P
Brück
Klaus
K
Badenhoop
Stefan
S
Zeuzem
Elizabeth
E
Ramos-Lopez
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
CYP24A1; CYP27B1; CYP2R1; Clear cell renal cell carcinoma; vitamin D