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 osteosarcoma, breast carcinoma, and colon carcinoma cell lines has been described. In this study, the level of vitamin D receptor was analyzed in a panel of colon adenoma and adenocarcinoma cell lines and the receptor level was correlated with the response to treatment with 1,25-dihydroxyvitamin D3. Ribonuclease protection and ligand-binding assays quantitated the level of vitamin D receptor mRNA expression and the level of functional receptors, respectively. The more well-differentiated cell lines, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, clonogenic assay, and growth curve study in HT29 and SW620 cell lines assessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at concentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, but growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent normal tissue, and in 9 cases, the tumor expressed a lower vitamin D receptor level. Our results suggest that the level of vitamin D receptor correlates with the degree of differentiation in human colon cancer cell lines and may serve as a useful biological marker in predicting clinical outcome in patients.
Department of Surgery, Lombardi Research Cancer Center, Georgetown University Hospital, Washington, DC 20007.
M
M
Shabahang
R R
RR
Buras
F
F
Davoodi
L M
LM
Schumaker
R J
RJ
Nauta
S R
SR
Evans
D000236:Adenoma / Q000737:chemistry; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol