Clonal differences in expression of 25-hydroxyvitamin D(3)-1alpha-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 1alpha,25-dihydroxyvitamin D(3).

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.

Bareis P ，Kállay E ，Bischof MG ，Bises G ，Hofer H ，Pötzi C ，Manhardt T ，Bland R ，Cross HS ... -  《EXPERIMENTAL CELL RESEARCH》

Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase, 1,25-dihydroxyvitamin D3 24-hydroxylase and vitamin D receptor gene expression by 8-bromo cyclic AMP in cultured human syncytiotrophoblast cells.

Avila E ，Díaz L ，Halhali A ，Larrea F ... -  《JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY》

Expression and activity of vitamin D-metabolizing cytochrome P450s (CYP1alpha and CYP24) in human nonsmall cell lung carcinomas.

Jones G ，Ramshaw H ，Zhang A ，Cook R ，Byford V ，White J ，Petkovich M ... -  《ENDOCRINOLOGY》

Altered pharmacokinetics of 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 in the blood and tissues of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) null mouse.

Masuda S ，Byford V ，Arabian A ，Sakai Y ，Demay MB ，St-Arnaud R ，Jones G ... -  《ENDOCRINOLOGY》

Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.

Diesel B ，Radermacher J ，Bureik M ，Bernhardt R ，Seifert M ，Reichrath J ，Fischer U ，Meese E ... -  《CLINICAL CANCER RESEARCH》