1,25-DIHYDROXYVITAMIN-D3 RECEPTOR AS A MARKER OF HUMAN COLON-CARCINOMA CELL-LINE DIFFERENTIATION AND GROWTH-INHIBITION

The antiproliferative action of 1,25-dihydroxyvitamin D3 in osteosarco ma, breast carcinoma, and colon carcinoma cell lines has been describe d. In this study, the level of vitamin D receptor was analyzed in a pa nel of colon adenoma and adenocarcinoma cell lines and the receptor le vel was correlated with the response to treatment with 1,25-dihydroxyv itamin D3. Ribonuclease protection and ligand-binding assays quantitat ed the level of vitamin D receptor mRNA expression and the level of fu nctional receptors, respectively. The more well-differentiated cell li nes, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, c lonogenic assay, and growth curve study in HT29 and SW620 cell lines a ssessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at co ncentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, bu t growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent nor mal tissue, and in 9 cases, the tumor expressed a lower vitamin D rece ptor level. Our results suggest that the level of vitamin D receptor c orrelates with the degree of differentiation in human colon cancer cel l lines and may serve as a useful biological marker in predicting clin ical outcome in patients.