Oncogene Effects on Glucocorticoid Regulation of Gene Expression

v-mos癌蛋白对糖皮质激素诱导金属硫蛋白-1 （Mt-1）基因表达的影响已经在大鼠6m2细胞系中进行了评估，其中p85gag- mos癌基因的表达及其转化是温度敏感的（ts）。p85gag-mos致癌基因及其转化对温度敏感。p85gag-mos在6m2细胞中的温度依赖性表达只导致短暂的地塞米松诱导Mt-1水平，尽管激素持续存在，但Mt-1水平迅速下降到非诱导水平。将进行核连续试验，以确定Mt-1 mRNA水平的瞬时诱导在多大程度上反映了v-mos对转录的影响。通过温度转移实验和激素戒断和再刺激来检测脱敏Mt- 1表达的动力学和可逆性，将揭示v-mos是否加速了“正常”的脱诱导过程，还是影响了独立的脱敏途径。糖皮质激素调节内源性和转染基因的阳性和阴性表达将在各种ts -mos转化细胞类型中进行分析。这些分析将决定是否癌蛋白效应可以区分可能是细胞类型特异性和受多激素控制的激素反应。它们还将允许在v-mos介导的激素调节基因表达的改变和糖皮质激素受体功能之间存在关联（如果存在的话）。

The effects of a v-mos oncoprotein on glucocorticoid-induction of metallothionein-1 (Mt-1) gene expression have been evaluated using the rat 6m2 cell line, in which expression of the p85gag- mos oncogene, and consequently transformation, are temperature- sensitive (ts). The p85gag-mos oncogene, and consequently transformation, are temperature-sensitive (ts). The temperature-dependent expression of p85gag-mos in 6m2 cells resulted in only a transient dexamethasone induction of Mt-1 levels, that rapidly declined to uninduced levels despite the continued presence of hormone. Nuclear run-on assays will be performed to determine to what extent transient induction of Mt-1 mRNA levels reflect v-mos effects on transcription. The examination of the kinetics and reversibility of desensitized Mt- 1 expression, using both temperature-shift experiments and hormone withdrawal and restimulation, will reveal whether v-mos accelerates a "normal" deinduction process or affects an independent desensitization pathway. Glucocorticoid regulated expression, both positive and negative of endogenous and transfected genes will be analyzed in various ts v-mos- transformed cell types. These analyses will determine whether oncoprotein effects can be distinguished for hormonal responses that may be cell type specific and subject to multi-hormonal control. They will also allow corrorlations, if any exist, between v-mos mediated alterations in hormone regulated gene expression and glucocorticoid receptor function.