Tanaka H, Dong Y, McGuire J, Okret S, Poellinger L, Makino I, Gustafsson J A
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
J Biol Chem. 1993 Jan 25;268(3):1854-9.
Signal transduction by glucocorticoid hormones is mediated by the intracellular glucocorticoid receptor protein. The mechanisms determining cell type- or tissue-specific differences in hormone responsiveness remain, however, unclear. To address this issue we have used two different rat hepatoma cell lines, 762 and 6.10.2, respectively, in which mouse mammary tumor virus has been stably integrated. Nuclear extracts from both of these cell lines contained a factor that bound to a sequence motif extending from -163 to -147 in the mouse mammary tumor virus promoter and that appeared to repress hormonal induction of viral mRNA expression. Transient transfection experiments indicated that the cellular levels of this putative repressor did not affect basal promoter activity; this factor appeared rather to determine cellular sensitivity to glucocorticoids. Moreover, in these experiments the relative levels of the glucocorticoid receptor appeared to be the main determinant of maximum inducibility of virus expression by hormone. Taken together, these data indicate that the differential expression patterns of receptor versus the putative repressor protein may determine the level of hormonal responsiveness of target genes in glucocorticoid-sensitive tissues.
糖皮质激素的信号转导由细胞内糖皮质激素受体蛋白介导。然而，决定细胞类型或组织特异性激素反应差异的机制仍不清楚。为了解决这个问题，我们分别使用了两种不同的大鼠肝癌细胞系，762和6.10.2，其中小鼠乳腺肿瘤病毒已稳定整合。这两种细胞系的核提取物都含有一种因子，该因子与小鼠乳腺肿瘤病毒启动子中从-163延伸至-147的序列基序结合，并且似乎抑制病毒mRNA表达的激素诱导。瞬时转染实验表明，这种假定的阻遏物的细胞水平不影响基础启动子活性；该因子似乎反而决定了细胞对糖皮质激素的敏感性。此外，在这些实验中，糖皮质激素受体的相对水平似乎是激素诱导病毒表达最大诱导性的主要决定因素。综上所述，这些数据表明，受体与假定的阻遏蛋白的差异表达模式可能决定糖皮质激素敏感组织中靶基因的激素反应水平。
