X RAY, HEAT SHOCK AND CELL CYCLE COUPLED GENE EXPRESSION

X 射线、热休克和细胞周期偶联基因表达

• 批准号: 6173397
• 负责人: Prabhat C Goswami
• 金额: $ 10.29万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173397
• 关键词: DNA topoisomerases; X ray; cell cycle; gene expression; genetic transcription; hyperthermia; messenger RNA; nuclear runoff assay; radiation genetics; tissue /cell culture

DESCRIPTION: (adapted from the investigator's abstract) Tumor cell proliferation following treatment with ionizing radiation or hyperthermia is thought to be major determinant of therapeutic outcome in protocols utilizing these agents. Recent studies have shown that proliferation is controlled by the temporal expression of cell cycle coupled genes. These genes are regulated at multiple levels including both transcriptional and post-transcriptional mechanisms such as mRNA stability. The overall objective of the proposed research is to elucidate the mechanism of x-irradiation and hyperthermia-induced down regulation of cell cycle coupled genes specific to late S and G2-phases. Specifically these investigators will test the hypothesis that mRNA stability plays a significant role in the expression of topoisomerase IIalpha (TopoII) under these conditions. TopoII is a multifunctional protein required during replication, chromosome disjunction at mitosis and other DNA-related activities by virtue of its ability to alter DNA supercoiling. TopoII is maximally expressed in late S and G2- phases, and is down regulated by x-irradiation or heat shock, conditions which delay cell cycle progression. The mechanism by which specific sequences in the 3' untranslated region of the TopoII mRNA regulate turnover will be determined and the polypeptides which interact with those sequences will be identified. Finally, it will be determined if enhanced stability of TopoII mRNA increases the corresponding protein levels thus leading to altered G2-transit.

描述：（改编自研究者的摘要）肿瘤细胞 电离辐射或热疗治疗后的增殖 被认为是方案中治疗结果的主要决定因素 利用这些代理。 最近的研究表明，增殖是 由细胞周期耦合基因的时间表达控制。 这些 基因在多个层面上受到调控，包括转录和 转录后机制，例如 mRNA 稳定性。 整体 拟议研究的目的是阐明其机制 X 射线照射和热疗诱导的细胞周期下调 特定于晚期 S 和 G2 期的基因。 具体来说，这些调查人员 将检验 mRNA 稳定性在 拓扑异构酶 IIα (TopoII) 在这些条件下的表达。 拓扑异构酶II 是复制过程中所需的多功能蛋白质，染色体 有丝分裂和其他 DNA 相关活动的分离凭借其 改变 DNA 超螺旋的能力。 TopoII 在 S 晚期表达最大 和 G2- 相，并通过 x 辐射或热休克下调， 延迟细胞周期进程的条件。 其机制 TopoII mRNA 3'非翻译区的特定序列调节 将确定周转率以及与这些周转率相互作用的多肽 序列将被识别。 最后确定是否增强 TopoII mRNA 的稳定性增加了相应的蛋白质水平，从而 导致 G2 转运改变。

项目成果

Proto-oncogene mRNA levels and activities of multiple transcription factors in C3H 10T1/2 murine embryonic fibroblasts exposed to 835.62 and 847.74 MHz cellular phone communication frequency radiation

• DOI: 10.2307/3579942
• 发表时间: 1999-03-01
• 期刊: RADIATION RESEARCH
• 影响因子: 3.4
• 作者: Goswami, PC;Albee, LD;Hunt, CR
• 通讯作者: Hunt, CR