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
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
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DOI：
10.1002/ijc.2910620611
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发表时间：
1995-09-15
影响因子：
6.4
通讯作者：
CROSS, HS
中科院分区：
文献类型：
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作者：
HULLA, W;KALLAY, E;CROSS, HS
人结肠癌细胞系Caco-2虽然是恶性起源的，但仍然能够以可调节的方式表达c-myc原癌基因。从对数生长期过渡到静止期，即，融合状态，伴随着细胞周期G（0）/G（1）期细胞数量的显著增加，以及伴随的c-myc mRNA和c-myc蛋白核结合的减少。相反，通过将细胞外[Ca++]（0）降低至0.25 mM的生长刺激导致c-myc表达水平上调，并因此抑制Caco-2细胞重新进入G（0）/G（1）期。相反，Caco-2细胞中c-myc的调节对维生素D甾醇完全耐受，因为1 α，25-二羟基维生素D-3的抗有丝分裂作用（1 α，25（OH）（2）D-3）和2种合成类似物1 α，25（OH）（2）-16-烯-23-炔-D-3和1 α，25（OH）（2）-26，27-F-6-16-烯-23-炔-D-3，c-myc mRNA和核蛋白水平的任何变化都是独立的。虽然维生素D固醇的抗增殖作用需要与细胞质维生素D受体（VDR）的高亲和力结合，但维生素D固醇对Caco-2细胞中的VDR mRNA水平没有影响。然而，VDR mRNA表达的变化在一个反平行的方式，c-myc的调节后，在不同的生长状态之间的过渡。这表明VDR mRNA丰度对于Caco-2细胞中维生素D相关的c-myc非依赖性生长控制仍然是重要的。(C)1995 Wiley-Liss，Inc.
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.