Vitamin D hydroxylases CYP2R1, CYP27B1 and CYP24A1 in renal cell carcinoma

Authors

  • Anja Urbschat,

    Corresponding author
    1. Faculty of Medicine, Goethe University Hospital, Frankfurt am Main, Germany
    • Correspondence to: Anja Urbschat, Faculty of Medicine, Goethe University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Tel.: + 49 69-6301-87821; fax: + 49 69 95119641; e-mail: Urbschat@med.uni-frankfurt.de

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  • Patrick Paulus,

    1. Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe University Hospital, Frankfurt am Main, Germany
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  • Quirine Freiin von Quernheim,

    1. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, Frankfurt am Main, Germany
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  • Patrick Brück,

    1. Department of Internal Medicine IV, Division of Hematology and Oncology, University Hospital of Giessen, Giessen, Germany
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  • Klaus Badenhoop,

    1. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, Frankfurt am Main, Germany
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  • Stefan Zeuzem,

    1. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, Frankfurt am Main, Germany
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  • Elizabeth Ramos-Lopez

    1. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, Frankfurt am Main, Germany
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Abstract

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)2D3), 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)2D3, which is synthesized in the proximal renal tubules.

Materials and 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).

Conclusion

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.

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