GROWTH-CONTROL OF HUMAN COLON-ADENOCARCINOMA-DERIVED CACO-2 CELLS BY VITAMIN-D COMPOUNDS AND EXTRACELLULAR CALCIUM IN-VITRO - RELATION TO C-MYC-ONCOGENE AND VITAMIN-D-RECEPTOR EXPRESSION

被引:38
作者
HULLA, W [1 ]
KALLAY, E [1 ]
KRUGLUGER, W [1 ]
PETERLIK, M [1 ]
CROSS, HS [1 ]
机构
[1] UNIV VIENNA,SCH MED,DEPT GEN & EXPTL PATHOL,A-1090 VIENNA,AUSTRIA
关键词
D O I
10.1002/ijc.2910620611
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The human colon-cancer cell line Caco-2, though of malignant origin, is still able to express the c-myc proto-oncogene in a regulable fashion. Transition from the logarithmic growth phase into the quiescent, i.e., confluent state, is accompanied by a significant increase in the number of cells in the G(0)/G(1) phase of the cell cycle and a concomitant reduction of c-myc mRNA and of nuclear association of c-myc protein. Conversely, growth stimulation by lowering extracellular [Ca++](0) to 0.25 mM results in up-regulation of c-myc expression levels and consequently inhibition of re-entry of Caco-2 cells into the G(0)/G(1) phase. In contrast, regulation of c-myc in Caco-2 cells is completely resistant to vitamin-D sterols, since the anti-mitogenic action of 1 alpha,25-dihdroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) and of 2 synthetic analogs, 1 alpha,25(OH)(2)-16-ene-23-yne-D-3 and 1 alpha,25(OH)(2)-26,27-F-6-16-ene-23-yne-D-3, occured independently of any change in c-myc mRNA and nuclear protein levels. Although the antiproliferative effect of the vitamin-D sterols requires high-affinity binding to the cytoplasmic vitamin-D receptor (VDR), vitamin-D sterols have no effect on VDR mRNA levels in Caco-2 cells. However, VDR mRNA expression changed in an antiparallel fashion to c-myc regulation upon transition between different growth states. This suggests that VDR mRNA abundance could nevertheless be important for vitamin-D-related c-myc-independent growth control in Caco-2 cells. (C) 1995 Wiley-Liss, Inc.
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页码:711 / 716
页数:6
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