Oncogene Effects on Glucocorticoid Regulation of Gene Expression

癌基因对糖皮质激素基因表达调节的影响

• 批准号: 8902897
• 负责人: Donald Benedict DeFranco
• 金额: $ 32.79万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8902897&HistoricalAwards=false
• 关键词: Oncogene; Effects; Glucocorticoid; Regulation; Gene

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.

v-mos癌蛋白对糖皮质激素诱导的人肝癌细胞凋亡的影响 金属硫蛋白-1（Mt-1）基因表达已被评估 使用大鼠6 m2细胞系，其中表达p85 gag- mos癌基因，以及随之而来的转化，是温度- 敏感（ts）。 p85 gag-mos癌基因，因此 相变是温度敏感的（Ts）。 的 p85 gag-mos在6 m2细胞中表达温度依赖性 仅导致Mt-1的短暂地塞米松诱导 水平，迅速下降到未诱导的水平，尽管 激素的持续存在。 核试验将是 以确定Mt-1的瞬时诱导程度 mRNA水平反映了v-mos对转录的影响。 的 检测脱敏的MT的动力学和可逆性， 1表达，使用温度变化实验和 激素的撤回和再刺激，将揭示是否v-mos 加速“正常”的反感应过程或影响 独立的脱敏途径。 糖皮质激素调节 表达，阳性和阴性的内源性和 转染的基因将在各种TSV-MOS中进行分析， 转化的细胞类型 这些分析将确定癌蛋白的作用是否可以 以可能是细胞类型的激素反应而区分 特异性和受多种激素控制。 他们还将 允许v-mos介导的 激素调节基因表达的改变， 糖皮质激素受体功能