The candidate oncogene CYP24A1: A potential biomarker for colorectal tumorigenesis

J Histochem Cytochem. 2010 Mar;58(3):277-85. doi: 10.1369/jhc.2009.954339. Epub 2009 Nov 9.

Abstract

The main autocrine/paracrine role of the active metabolite of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), 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 D(3) 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D(3), 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-D(3) availability, decreasing its antiproliferative effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Messenger / biosynthesis
  • Receptors, Calcitriol / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroid Hydroxylases / biosynthesis*
  • Steroid Hydroxylases / genetics
  • Vitamin D3 24-Hydroxylase

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • RNA, Messenger
  • Receptors, Calcitriol
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase