This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matusiak, D. Articles by Benya, R. V. Search for Related Content PubMed PubMed Citation Articles by Matusiak, D. Articles by Benya, R. V. Related Collections Oncogenesis Oncogenesis: Biomarkers

Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1-Hydroxylase in Normal and Malignant Human Colon

¹ Department of Medicine, University of Illinois at Chicago; ² Jessie Brown Veterans Administration Medical Center; and ³ Carcinogenesis and Chemoprevention Division, Illinois Institute of Technology Research Institute, Chicago, Illinois

Requests for reprints: Richard V. Benya, Department of Medicine, University of Illinois at Chicago, 840 South Wood Street (M/C 716), Chicago, IL 60612. Phone: 312-569-7439; Fax: 312-569-8114. E-mail: rvbenya{at}uic.edu

Considerable evidence exists to support the use of vitamin D to prevent and/or treat colorectal cancer. However, the routine use of bioactive vitamin D, 1,25-dihydroxyvitamin D3, is limited by the side effect of toxic hypercalcemia. Recent studies, however, suggest that colonic epithelial cells express 25-hydroxyvitamin D3-1-hydroxylase, an enzyme that converts nontoxic pro-vitamin D, 25-hydroxycholecalciferol [25(OH)D3], to its bioactive form. Yet, nothing is known as to the cellular expression of 1-hydroxylase and the vitamin D receptor (VDR) in the earliest histopathologic structures associated with malignant transformation such as aberrant crypt foci (ACF) and polyps [addressing the possibility of using nontoxic 25(OH)D3 for chemoprevention], nor is anything known as to the expression of these proteins in colorectal cancer as a function of tumor cell differentiation or metastasis [relevant to using 25(OH)D3 for chemotherapy]. In this study, we show that 1-hydroxylase is present at equal high levels in normal colonic epithelium as in ACFs, polyps, and colorectal cancer irrespective of tumor cell differentiation. In contrast, VDR levels were low in normal colonic epithelial cells; were increased in ACFs, polyps, and well-differentiated tumor cells; and then declined as a function of tumor cell de-differentiation. Both 1-hydroxylase and VDR levels were negligible in tumor cells metastasizing to regional lymph nodes. Overall, these data support using 25(OH)D3 for colorectal cancer chemoprevention but suggest that pro-vitamin D is less likely to be useful for colorectal cancer chemotherapy.

This article has been cited by other articles:

				S. Pilz, H. Dobnig, B. Winklhofer-Roob, G. Riedmuller, J. E. Fischer, U. Seelhorst, B. Wellnitz, B. O. Boehm, and W. Marz Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1228 - 1233. [Abstract] [Full Text] [PDF]

				D. Matusiak and R. V. Benya CYP27A1 and CYP24 Expression as a Function of Malignant Transformation in the Colon J. Histochem. Cytochem., December 1, 2007; 55(12): 1257 - 1264. [Abstract] [Full Text] [PDF]

				L. Taglia, D. Matusiak, K. A. Matkowskyj, and R. V. Benya Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by upregulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G182 - G190. [Abstract] [Full Text] [PDF]