The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis

The main autocrine/paracrine role of the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25-D3), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or...

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Bibliographic Details
Published in:The journal of histochemistry and cytochemistry 2010-03, Vol.58 (3), p.277-285
Main Authors: Horvath, Henrik C, Lakatos, Peter, Kosa, Janos P, Bacsi, Krisztian, Borka, Katalin, Bises, Giovanna, Nittke, Thomas, Hershberger, Pamela A, Speer, Gabor, Kallay, Eniko
Format: Article
Language:English
Subjects:
Adenocarcinoma - enzymology
Adenocarcinoma - pathology
Adenoma - enzymology
Adenoma - pathology
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - biosynthesis
Cell Proliferation
Colon - enzymology
Colorectal Neoplasms - enzymology
Colorectal Neoplasms - pathology
Female
Humans
Immunohistochemistry
Intestinal Mucosa - enzymology
Ki-67 Antigen - biosynthesis
Male
Middle Aged
Receptors, Calcitriol - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
Steroid Hydroxylases - biosynthesis
Steroid Hydroxylases - genetics
Vitamin D3 24-Hydroxylase
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Summary:The main autocrine/paracrine role of the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25-D3), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D3, we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D3 availability, decreasing its antiproliferative effect.
ISSN:0022-1554
1551-5044
DOI:10.1369/jhc.2009.954339