Schmidt C J, Hamer D H
Proc Natl Acad Sci U S A. 1986 May;83(10):3346-50. doi: 10.1073/pnas.83.10.3346.
The expression of three human metallothionein (hMT) genes has been compared in various established cell lines and primary liver. The single gene for hMT isoform II is ubiquitously expressed in all cell types in response to cadmium. In contrast, two genes encoding hMT-I isoforms are expressed in a highly specific, reciprocal fashion that correlates with the embryonic germ layer origin of the cells. In one cell line that failed to express detectable amounts of hMT-IE, treatment with the demethylating agent 5-azacytidine led to cadmium-inducible expression of this subtype. The genes for both MT-I isoforms are coordinately inducible by heavy metals but differ in their response to glucocorticoids. Surprisingly, cells transformed with the Ha-ras oncogene contain elevated basal levels of both MT-I and MT-II RNA. The implications of these results for growth-related and developmental functions of MT are discussed.
已对三种人类金属硫蛋白（hMT）基因在各种已建立的细胞系和原代肝脏中的表达进行了比较。hMT同工型II的单个基因在所有细胞类型中均对镉作出反应而普遍表达。相比之下，编码hMT-I同工型的两个基因以高度特异性的相互方式表达，这与细胞的胚胎胚层起源相关。在一个未能表达可检测量的hMT-IE的细胞系中，用去甲基化剂5-氮杂胞苷处理导致该亚型的镉诱导表达。两种MT-I同工型的基因均可被重金属协同诱导，但对糖皮质激素的反应不同。令人惊讶的是，用Ha-ras癌基因转化的细胞中MT-I和MT-II RNA的基础水平均升高。讨论了这些结果对MT的生长相关和发育功能的影响。
