1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms

Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy.