Tong W M, Kállay E, Hofer H, Hulla W, Manhardt T, Peterlik M, Cross H S
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Eur J Cancer. 1998 Dec;34(13):2119-25. doi: 10.1016/s0959-8049(98)00267-6.
The human colon adenocarcinoma-derived cell line Caco-2 was used as a model system to study the interaction of epidermal growth factors (EGF) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in control of colorectal cancer cell growth. The mitogenic stimulus of EGF was rapidly transduced via apical and basal membrane receptors alike into elevation of c-myc expression, causing a shift of Caco-2 cells from the G0/G1 into the S phase of the cell cycle. The stimulatory effect of EGF on cell division was effectively counteracted by 1,25(OH)2D3: the presence of the steroid hormone prevents the negative effect of EGF on vitamin D receptor abundance and concurrently minimises ligand-occupied EGF receptor numbers on both sides of Caco-2 cell monolayers. Our data suggest that EGF and 1,25-(OH)2D3 actions on mutual receptor levels represent a specific feature of the potent antimitogenic effect of the steroid hormone on colon cancer cells.
人结肠腺癌来源的细胞系Caco-2被用作模型系统,以研究表皮生长因子(EGF)和1,25-二羟基维生素D3(1,25(OH)2D3)在控制结肠癌细胞生长中的相互作用。EGF的促有丝分裂刺激通过顶端和基底膜受体迅速转导,导致c-myc表达升高,使Caco-2细胞从G0/G1期进入细胞周期的S期。1,25(OH)2D3有效地抵消了EGF对细胞分裂的刺激作用:类固醇激素的存在可防止EGF对维生素D受体丰度的负面影响,同时使Caco-2细胞单层两侧配体占据的EGF受体数量降至最低。我们的数据表明,EGF和1,25-(OH)2D3对相互受体水平的作用代表了类固醇激素对结肠癌细胞强大的抗有丝分裂作用的一个特定特征。