Carcinogenesis Advance Access originally published online on May 19, 2005
Carcinogenesis 2005 26(9):1581-1589; doi:10.1093/carcin/bgi124
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis vol.26 no.9 © Oxford University Press 2005; all rights reserved.
Colon-specific regulation of vitamin D hydroxylases—a possible approach for tumor prevention
Department of Pathophysiology, 1 Department of Medical and Chemical Laboratory Diagnostics and 2 Center for Animal Care, Medical University of Vienna, A-1090 Vienna, Währinger Guertel 18-20, Austria, 3 Institute of Analytical Chemistry, University of Vienna, Währinger Strasse 38, A-1090 Vienna, Austria, 4 Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Japan and 5 Geriatric Research, Education, and Clinical Center, St Louis Veterans Administration Medical Center, St Louis, MO 63125, USA
* To whom correspondence should be addressed. Tel: +43 1 40400 5123; Fax: +43 1 40400 5130; Email: heide.cross{at}meduniwien.ac.at
Epidemiological data suggest a protective role of calcium and vitamin D against colorectal tumor pathogenesis. 1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis, cell proliferation and differentiation. Calcium in the intestinal lumen functions as a growth regulator and may prevent cancer by direct reduction of colonocyte proliferation. While calcium or vitamin D can counteract proliferation by itself, they could also interact if nutritional calcium were to modulate colonic vitamin D synthesis. In this paper we demonstrate that colonic and renal vitamin D hydroxylases are regulated independently. When mice were fed a modified AIN-76 diet containing low dietary calcium (0.1 or 0.04%) fecal calcium content was as low as 5% of that found in mice on a 0.9% calcium containing diet. Low fecal calcium concentration enhanced proliferating cell nuclear antigen expression in the colon mucosa and reduced that of the cyclin dependent kinase inhibitor p21. While low dietary calcium did not affect colonic expression of VDR or 25-hydroxyvitamin D3 1
-hydroxylase (CYP27B1) mRNA, it influenced their renal expression in the expected manner by elevating the CYP27B1 expression and reducing VDR and 25-hydroxyvitamin D3 24-hydroxylase (CYP24) expression. In contrast, low calcium diets significantly augmented colonic CYP24 mRNA expression, but only in the ascending colon. This might result in reduced colonic accumulation of 1,25-D3 during hyperproliferation caused by low dietary calcium and might support site-specific tumorigenesis. The important realization that low dietary calcium by itself is a risk factor for colorectal carcinogenesis and that colonic and renal vitamin D hydroxylases indeed are regulated differently from each other will provide novel approaches for colon cancer prevention.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. PETERLIK, W. B. GRANT, and H. S. CROSS Calcium, Vitamin D and Cancer Anticancer Res, September 1, 2009; 29(9): 3687 - 3698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. CROSS, T. NITTKE, and M. PETERLIK Modulation of Vitamin D Synthesis and Catabolism in Colorectal Mucosa: A New Target for Cancer Prevention Anticancer Res, September 1, 2009; 29(9): 3705 - 3712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. NITTKE, E. KALLAY, T. MANHARDT, and H. S. CROSS Parallel Elevation of Colonic 1,25-Dihydroxyvitamin D3 Levels and Apoptosis in Female Mice on a Calcium-deficient Diet Anticancer Res, September 1, 2009; 29(9): 3727 - 3732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chakraborty, P. C. Maity, A. K. Sil, Y. Takeda, and S. Das cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor J. Biol. Chem., August 14, 2009; 284(33): 21810 - 21827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Protiva, H. S. Cross, M. E. Hopkins, E. Kallay, G. Bises, E. Dreyhaupt, L. Augenlicht, M. Lipkin, M. Lesser, E. Livote, et al. Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity Cancer Prevention Research, January 1, 2009; 2(1): 43 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S Cross Commentary: From epidemiology to molecular biology--vitamin D and colorectal cancer prevention Int. J. Epidemiol., April 1, 2006; 35(2): 225 - 227. [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Cross, M. Lipkin, and E. Kallay Nutrients Regulate the Colonic Vitamin D System in Mice: Relevance for Human Colon Malignancy J. Nutr., March 1, 2006; 136(3): 561 - 564. [Abstract] [Full Text] [PDF]
|
|