Endonuclease deficiency in breast cancer progression

乳腺癌进展中核酸内切酶缺乏

• 批准号: 7049687
• 负责人: Alexei G Basnakian
• 金额: $ 6.3万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049687
• 关键词: DNA replication; MCF7 cell; RNA interference; apoptosis; biomarker; breast neoplasms; cell differentiation; endonuclease; enzyme activity; enzyme deficiency; enzyme induction /repression; enzyme linked immunosorbent assay; estrogen receptors; genetic regulation; molecular oncology; neoplasm /cancer invasiveness; neoplastic cell; polymerase chain reaction; progesterone receptors; receptor expression; transfection /expression vector; vimentin; western blottings

DESCRIPTION (provided by applicant): Endonuclease-mediated DMA strand breaks interfere with replication, induce apoptotic DMA fragmentation and ultimately cell death. To the contrary, breast cancer progression is associated with decreased apoptosis, and an increased rate of DMA synthesis. This discrepancy could be explained by a deficiency of an endonuclease in poorly differentiated invasive breast cancer cells. However, the concept that an endonuclease deficiency may be essential for breast cancer progression has not been previously considered, and a relationship between an endonuclease and cancer progression has not been examined. We hypothesize that EndoG deficiency is essential for the progression of breast cancer by limiting apoptosis, allowing high rate of DMA synthesis, and that EndoG deficiency can be used as a new biomarker for human breast cancer progression. The purpose of this study is to determine whether EndoG deficiency is a common phenomenon in breast cancer progression, and whether it is mechanistically linked to the breast cancer dediffefentiation and increased invasiveness. If according to our expectation, EndoG will be shown to be the cause of breast cancer progression, it may be used in the future as a very reliable biomarker of breast cancer progression. Our strategy will be first to examine EndoG regulation as a function of differentiation and invasiveness of breast cancer cells in Specific Aim 1. The next specific aim will be focused on functional studies to determine the role of EndoG in dedifferentiation and invasiveness of breast cancer cells in vitro (Specific Aim 2).

描述（由申请人提供）： 核酸内切酶介导的DMA链断裂会干扰复制，诱导凋亡DMA碎片并最终导致细胞死亡。相反，乳腺癌的进展与凋亡降低和DMA合成率增加有关。这种差异可以通过分化较差的侵入性乳腺癌细胞中核酸内切酶的缺乏来解释。但是，尚未考虑过核酸内切酶缺乏症可能是乳腺癌进展至关重要的概念，并且尚未检查核酸内切酶与癌症进展之间的关系。我们假设通过限制细胞凋亡，允许DMA合成率高，而内生症的缺乏症对于乳腺癌的进展至关重要，并且该内生缺乏症可以用作人类乳腺癌进展的新生物标志物。这项研究的目的是确定乳腺癌进展中的内ON缺乏症是否是一种常见现象，以及它是否与乳腺癌的脱脂性和侵入性增加有关。如果根据我们的预期，将证明内og被证明是乳腺癌进展的原因，将来可以用作乳腺癌进展的非常可靠的生物标志物。我们的策略将首先研究在特定目标中检查乳腺癌细胞的分化和侵入性的函数。下一个特定目标将集中在功能研究上，以确定内生的作用体外（特定目标2）。