Local production of active vitamin D 3 metabolites in breast cancer cells by CYP24A1 and CYP27B1.

Autor: Dennis C; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA., Dillon J; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA., Cohen DJ; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA., Halquist MS; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA; Bioanalytical Core Laboratory, Central Virginia Drug Abuse Research Center, Virginia Commonwealth University, Richmond, VA 23298, USA., Pearcy AC; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA., Schwartz Z; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA., Boyan BD; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: bboyan@vcu.edu.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2023 Sep; Vol. 232, pp. 106331. Date of Electronic Publication: 2023 May 25.
DOI: 10.1016/j.jsbmb.2023.106331
Abstrakt: The role of vitamin D 3 and its metabolites in cancer and especially as a treatment option has been widely disputed. Clinicians noting low serum 25-hydroxyvitamin D 3 [25(OH)D 3 ] levels in their patients, recommend vitamin D 3 supplementation as a method of reducing the risk of cancer; however, data supporting this are inconsistent. These studies rely on systemic 25(OH)D 3 as an indicator of hormone status, but 25(OH)D 3 is further metabolized in the kidney and other tissues under regulation by several factors. This study examined if breast cancer cells also possess the ability to metabolize 25(OH)D 3 , and if so, whether the resulting metabolites are secreted locally; if this ability reflects ERα66 status; and if they possess vitamin D receptors (VDR). To address this question, estrogen receptor alpha (ERα) positive (MCF-7) and ERα negative (HCC38 and MDA-MB-231) breast cancer cell lines were examined for expression of ERα66, ERα36, CYP24A1, CYP27B1, and VDR as well as for local production of 24,25-dihydroxyvitamin D 3 [24,25(OH) 2 D 3 ] and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] after treatment with 25(OH)D 3 . The results showed that independent of ER status, breast cancer cells express the enzymes CYP24A1 and CYP27B1, which are responsible for converting 25(OH)D 3 into its dihydroxylated forms. Moreover, these metabolites are produced at levels comparable to the levels observed in blood. They are positive for VDR, indicating that they can respond to 1α,25(OH) 2 D 3 , which can upregulate CYP24A1. These findings suggest that vitamin D metabolites may contribute to the tumorigenicity of breast cancer via autocrine and/or paracrine mechanisms.
Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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