Increased copy-number and not DNA hypomethylation causes overexpression of the candidate proto-oncogene CYP24A1 in colorectal cancer.
Höbaus J, Hummel DM, Thiem U, Fetahu IS, Aggarwal A, Müllauer L, Heller G, Egger G, Mesteri I, Baumgartner-Parzer S, Kallay E.
Int J Cancer. 2013 Sep 15;133(6):1380-8. doi: 10.1002/ijc.28143. Epub 2013 Apr 5.
Epidemiological studies suggest that high vitamin D might protect against colorectal cancer. Vitamin D and its active metabolites are degraded by 1,25 dihydroxyvitamin D 24 hydroxylase encoded by the CYP24A4 gene.
CYP24A1 is overexpressed in a variety of tumours; however, the mechanisms behind this overexpression are poorly understood. We demonstrate in this paper that one of the mechanisms behind CYP24A1 overexpression in colorectal tumours is increased copy number of the CYP24A1 gene. Interestingly this could be caused not only by gene amplification but also by polysomy of chromosome 20. We demonstrated that in colorectal tumours CAP24A1 expression is independent of the methylation status of its promoter. Furthermore, CYP24A1 expression correlates strongly with proliferation markers, suggestive of a causal relationship. CYP24A1 overexpression suppresses local vitamin D levels and thereby likely counteracts the anti-proliferative actions of active vitamin D possibly resulting in increased proliferation in tumours.
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