Novoselov Sergey V, Calvisi Diego F, Labunskyy Vyacheslav M, Factor Valentina M, Carlson Bradley A, Fomenko Dmitri E, Moustafa Mohamed E, Hatfield Dolph L, Gladyshev Vadim N
Department of Biochemistry, University of Nebraska, N 151 Beadle Center, 1901 Vine Street, Lincoln, NE 68588, USA.
Oncogene. 2005 Dec 1;24(54):8003-11. doi: 10.1038/sj.onc.1208940.
The micronutrient element selenium (Se) has been shown to be effective in reducing the incidence of cancer in animal models and human clinical trials. Selenoproteins and low molecular weight Se compounds were implicated in the chemopreventive effect, but specific mechanisms are not clear. We examined the role of Se and selenoproteins in liver tumor formation in TGFalpha/c-Myc transgenic mice, which are characterized by disrupted redox homeostasis and develop liver cancer by 6 months of age. In these mice, both Se deficiency and high levels of Se compounds suppressed hepatocarcinogenesis. In addition, both treatments induced expression of detoxification genes, increased apoptosis and inhibited cell proliferation. Within low-to-optimal levels of dietary Se, tumor formation correlated with expression of most selenoproteins. These data suggest that changes in selenoprotein expression may either suppress or promote tumorigenesis depending on cell type and genotype. Since dietary Se may have opposing effects on cancer, it is important to identify the subjects who will benefit from Se supplementation as well as those who will not.
微量营养素元素硒（Se）已被证明在动物模型和人体临床试验中能有效降低癌症发病率。硒蛋白和低分子量硒化合物被认为与化学预防作用有关，但具体机制尚不清楚。我们研究了硒和硒蛋白在TGFα/c-Myc转基因小鼠肝脏肿瘤形成中的作用，这些小鼠的特点是氧化还原稳态被破坏，6个月大时会发生肝癌。在这些小鼠中，缺硒和高剂量硒化合物均抑制肝癌发生。此外，两种处理均诱导解毒基因表达、增加细胞凋亡并抑制细胞增殖。在低至最佳膳食硒水平范围内，肿瘤形成与大多数硒蛋白的表达相关。这些数据表明，硒蛋白表达的变化可能根据细胞类型和基因型抑制或促进肿瘤发生。由于膳食硒可能对癌症有相反作用，因此确定哪些受试者将从补充硒中获益以及哪些不会获益很重要。
