25-Hydroxyvitamin D(3)-1alpha-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis

Abstract

Human colorectal cancer cells not only express the nuclear vitamin D receptor (VDR) but are also endowed with 25-hydroxy-vitamin D(3)-1alpha-hydroxylase activity and therefore are able to produce the specific ligand for the VDR, the hormonally active steroid 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)). In the present study we show by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) as well as by Western blotting and immunohistochemical methods, that in human large intestinal carcinomas expression of the genes encoding the 25-(OH)D(3)-1alpha-hydroxylase as well as the VDR increases in parallel with ongoing dedifferentiation in the early phase of cancerogenesis, whereas in poorly differentiated late stage carcinomas only low levels of the respective mRNAs can be detected. This indicates that, through up-regulation of this intrinsic 1alpha,25(OH)(2)D(3)/VDR system which mediates the anti-mitotic effects of the steroid hormone, colorectal cancer cells are apparently able to increase their potential for an autocrine counter-regulatory response to neoplastic cell growth, particularly in the early stages of malignancy.