CYP24A1 splice variants-Implications for the antitumorigenic actions of 1,25-(OH)2D3 in colorectal cancer

H. C. Horváth, Z. Khabir, T. Nittke, S. Gruber, G. Speer, T. Manhardt, E. Bonner, E. Kallay

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

25-Hydroxyvitamin D3 24-hydroxylase (CYP24A1), the catabolizing enzyme of the active vitamin D3, is often overexpressed in solid tumors. The unbalanced high levels of CYP24A1 seem to be a determinant of vitamin D resistance in tumors. Splice variants of CYP450 enzymes are common. Existence of CYP24A1 isoforms has been reported recently. We have investigated the presence of CYP24A1 splicing variants (SV) in human colon cancer cell lines and tissue samples. Using a set of primer combination we have screened the entire coding sequence of CYP24A1 and identified three splice variants in colon cancer cell lines. The presence of these SVs in human colon tissue samples showed a correlation with histological type of the tissue and gender of patients. The sequencing of the alternatively spliced fragments showed that two have lost the mitochondrial target domain, while the third lacks the heme-binding domain. All SVs retained their sterol binding domain. Translation of these variants would lead to a dysfunctional enzyme without catalytic activity that still binds its substrates therefore they might compete for substrate with the synthesizing and catabolizing enzymes of vitamin D.

Original languageEnglish
Pages (from-to)76-79
Number of pages4
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume121
Issue number1-2
DOIs
Publication statusPublished - Jul 2010

Fingerprint

Colorectal Neoplasms
Enzymes
Tissue
Vitamin D
Colonic Neoplasms
Tumors
Cells
Calcifediol
Cell Line
Cholecalciferol
Sterols
Substrates
Mixed Function Oxygenases
Heme
Catalyst activity
Neoplasms
Protein Isoforms
Colon
Vitamin D3 24-Hydroxylase

Keywords

  • Colorectal cancer
  • CYP24A1
  • Splicing variant
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry
  • Medicine(all)

Cite this

CYP24A1 splice variants-Implications for the antitumorigenic actions of 1,25-(OH)2D3 in colorectal cancer. / Horváth, H. C.; Khabir, Z.; Nittke, T.; Gruber, S.; Speer, G.; Manhardt, T.; Bonner, E.; Kallay, E.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 121, No. 1-2, 07.2010, p. 76-79.

Research output: Contribution to journalArticle

Horváth, H. C. ; Khabir, Z. ; Nittke, T. ; Gruber, S. ; Speer, G. ; Manhardt, T. ; Bonner, E. ; Kallay, E. / CYP24A1 splice variants-Implications for the antitumorigenic actions of 1,25-(OH)2D3 in colorectal cancer. In: Journal of Steroid Biochemistry and Molecular Biology. 2010 ; Vol. 121, No. 1-2. pp. 76-79.
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