Cross H S, Hulla W, Tong W M, Peterlik M
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
J Nutr. 1995 Jul;125(7 Suppl):2004S-2008S. doi: 10.1093/jn/125.suppl_7.2004S.
The Caco-2 cell line was utilized to analyze the role of nutrient factors such as calcium, vitamin D and epidermal growth factor (EGF) in epigenetic control of human colon carcinoma cell growth. Proliferative signals from either low extracellular calcium or EGF, respectively, are transduced in Caco-2 cells via an increase in c-myc proto-oncogene mRNA and nuclear protein expression levels. Activation of the EGF receptor is associated also with down-regulation of the cytoplasmic high-affinity vitamin D receptor (VDR). This would allow colon carcinoma cells to escape from the VDR-mediated anti-mitogenic action of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). However, Caco-2 cells have the unique property to synthesize the vitamin D hormone from 25-hydroxyvitamin D3. 1 alpha,25(OH)2D3, in turn, counteracts the negative effect of EGF on VDR abundancy and slow down tumor cell proliferation through a c-myc-independent pathway.
利用Caco-2细胞系分析钙、维生素D和表皮生长因子（EGF）等营养因子在人类结肠癌细胞生长的表观遗传控制中的作用。低细胞外钙或EGF的增殖信号分别通过c-myc原癌基因mRNA和核蛋白表达水平的增加在Caco-2细胞中传导。EGF受体的激活也与细胞质高亲和力维生素D受体（VDR）的下调有关。这将使结肠癌细胞逃避1α,25-二羟基维生素D3（1α,25(OH)2D3）的VDR介导的抗有丝分裂作用。然而，Caco-2细胞具有从25-羟基维生素D3合成维生素D激素的独特特性。反过来，1α,25(OH)2D3抵消了EGF对VDR丰度的负面影响，并通过一条不依赖c-myc的途径减缓肿瘤细胞增殖。
