In situ mRNA hybridization analysis and immunolocalization of the vitamin D receptor in normal and carcinomatous human colonic mucosa: relation to epidermal growth factor receptor expression

There is evidence that vitamin D receptor (VDR)-mediated action of 1 alpha ,25-dihydroxyvitamin D-3 (1 alpha ,25-(OH)(2)D-3) could limit colon cancer cell growth particularly when induced by activation of the epidermal growth factor receptor (EGFR). We therefore wanted to ascertain the relevance of this observation for human colon cancerogenesis. Utilizing in situ mRNA hyb ridization and immunocytochemical techniques, we analyzed cell-specific exp ression of VDR and EGFR in normal and malignant human colonic mucosa. In no rmal mucosa, VDR positivity is weak and observed only in a small number of luminal surface colonocytes. In contrast, EGFR expression at a relatively h igh level is also found in cells at the crypt base. The number of VDR-posit ive colonocytes increases remarkably during tumor progression. It reaches i ts maximum in low grade adenocarcinomas and returns to lower levels in high ly malignant cancers. In both low- and high grade carcinomas, the great maj ority of tumor cells contain the EGFR message. The relative abundance of EG FR over VDR in normal mucosa and in high grade carcinomas would create a si tuation in which mitogenic effects from EGFR activation are only ineffectiv ely counteracted by signaling from 1 alpha ,25-(OH)(2)D-3/VDR. In contrast, in well to moderately differentiated tumors, upregulation of VDR could ret ard further tumor progression.