caa a22 4500 477081002 CHVBK 20180405111449.0 cr unu---uuuuu 170330e19960101xx s 000 0 eng 10.1007/BF02722994 doi (NATIONALLICENCE)springer-10.1007/BF02722994 Altered distribution of the nuclear receptor rarβ accompanies proliferation and differentiation changes caused by retinoic acid in Caco-2 cells [Elektronische Daten] [Shirley McCormack, Mary Viar, Larry Tague, Leonard Johnson] Summary: All epithelial cells require retinoic acid for growth, maintenance, and differentiation. Although the epithelial cells that line the gastrointestinal tract are exposed to extreme retinoid concentration fluctuations in luminal fluid, whether proliferation and differentiation in these cells are significantly affected is not known. We have investigated this question using Caco-2 cells as a model because, although they are derived from a colon adenocarcinoma, they differentiate spontaneously in a manner similar to enterocytes in the small intestine. We found that retinoic acid caused maximum inhibition of cell growth and ornithine decarboxylase activity during the proliferative period. Retinoic acid increased brush border enzyme activities only in differentiating cells but stimulated transglutaminase activity in cells at all stages. In untreated proliferating cells, we found an early peak of transglutaminase activity that has not been reported before. Retinoic acid in intestinal cells acts through its nuclear receptor, RARβ. The nuclear distribution of this receptor has not been demonstrated. In this study, we show that RARβ responds to increasing concentrations of retinoic acid with a shift to the nuclear membrane in undifferentiated cells and progressive aggregation, diffusion, and loss in differentiated cells. We conclude that retinoic acid can inhibit proliferation and stimulate differentiation in Caco-2 cells depending on concentration and cell stage, and that these effects are accompanied by changes in distribution, as well as by the loss of RARβ. Society for In Vitro Biology, 1996 ODC, ornithine decarboxylase nationallicence TGA, transglutaminase nationallicence RA, retinoic acid nationallicence RARβ, retinoic acid receptor beta nationallicence McCormack Shirley Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut Viar Mary Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut Tague Larry Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut Johnson Leonard Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 32/1(1996-01-01), 53-61 1071-2690 32:1<53 1996 32 11626 https://doi.org/10.1007/BF02722994 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02722994 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McCormack Shirley Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut NATIONALLICENCE 700 1- Viar Mary Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut NATIONALLICENCE 700 1- Tague Larry Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut NATIONALLICENCE 700 1- Johnson Leonard Department of Physiology and Biophysics, University of Tennessee, 894 Union Avenue, 38163, Memphis, Tennessee aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 32/1(1996-01-01), 53-61 1071-2690 32:1<53 1996 32 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer