Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of Caco-2 cells.
The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or calcitriol, on the proliferation and differentiation of Caco-2 cells was studied. Vitamin D receptor mRNA was detected in both pre- and postconfluent cells, and its abundance was unchanged with time and in response to calcitriol. 1,25-(OH)2D3-binding activity increased during differentiation, but there was no difference in binding between 1,25-(OH)2D3-treated and control cells. 1,25-(OH)2D3 caused a dose-dependent reduction in proliferation, as assessed by [3H]thymidine incorporation and DNA content. 1,25-(OH)2D3 significantly enhanced the normal rise in alkaline phosphatase activity during differentiation and increased alkaline phosphatase mRNA abundance. In contrast, 1,25-(OH)2D3 inhibited the normal rise in sucrase-isomaltase activity and the corresponding mRNA level, although the inhibition occurred after the initial period of cell differentiation (> 10 days postplating). Morphological analysis demonstrated that by day 12 postplating, 1,25-(OH)2D3 increased the mean dome diameter and microvillus length and density. Although 1,25-(OH)2D3 decreases the proliferation of Caco-2 cells and enhances certain parameters of differentiation, not all brush-border hydrolases respond in a similar fashion, making it necessary to interpret with caution their individual use as markers of differentiation.
Halline
A G
AG
Section of Digestive and Liver Diseases, University of Illinois at Chicago 60612.
Davidson
N O
NO
Skarosi
S F
SF
Sitrin
M D
MD
Tietze
C
C
Alpers
D H
DH
Brasitus
T A
TA
D002117:Calcitriol / Q000032:analysis / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008854:Microscopy, Electron; D008871:Microvilli / Q000201:enzymology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics; D014407:Tumor Cells, Cultured
D003470:Culture Media; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol