UNSPECIFIED. (2002) Clonal differences in expression of 25-hydroxyvitamin D-3-1 alpha-hydroxylase, of 25-hydroxyvitamin D-3-24-hydroxylase, and of the vitamin D receptor in human colon carcinoma cells: Effects of epidermal growth factor and 1 alpha,25-dihydroxyvitamin D-3. EXPERIMENTAL CELL RESEARCH, 276 (2). pp. 320-327. ISSN 0014-4827

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Abstract

Human colon carcinoma cells express 25-hydroxyvitamin D-3-1alpha-hydroxylase (CYP27B1) and thus produce the vitamin D receptor (VDR) ligand 1alpha,25-dihydroxyvitamin D-3 (1,25-D3), which can be metabolized by 25-hydroxyvitamin D-3-24-hydroxylase (CYP24). Expression of VDR, CYP27B1, and CYP24 determines the efficacy of the antimitotic action of 1,25-D3 and is distinctly related to the degree of differentiation of cancerous lesions. In the present study we addressed the question of whether the effects of epidermal growth factor (EGF) and of 1,25-D3 on VDR, CYP27B1, and CYP24 gene expression in human colon carcinoma cell lines also depend on the degree of cellular differentiation. We were able to show that slowly dividing, highly differentiated Caco-2/15 cells responded in a dose-dependent manner to both EGF and 1,25-D3 by up-regulation of VDR and CYP27B1 expression, whereas in highly proliferative, less differentiated cell lines, such as Caco-2/AQ and COGA-1A and -1E, negative regulation was observed. CYP24 mRNA was inducible in all clones by 1,25-D3 but not by EGF. From the observed clonal differences in the regulatory effects of EGF and 1,25-D3 on VDR and CYP27B1 gene expression we suggest that VDR-mediated growth inhibition by 1,25-D3 would be efficient only in highly differentiated carcinomas even when under mitogenic stimulation by EGF. (C) 2002 Elsevier Science (USA).

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH301 Biology
Journal or Publication Title:	EXPERIMENTAL CELL RESEARCH
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN:	0014-4827
Date:	10 June 2002
Volume:	276
Number:	2
Number of Pages:	8
Page Range:	pp. 320-327
Identification Number:	10.1006/excr.2002.5528
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/10864

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