权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies of the mechanism for anchorage independent growth induced by c-myc

c-myc诱导贴壁独立生长机制的研究

基本信息

批准号：
10680678
负责人：
TSUNEOKA Makoto
金额：
$ 2.18万
依托单位：
KURUME UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680678/
关键词：
Myc Ras MEK MAPK Anchorage independent growth tumorigenesis apoptosis RCCl myc 細胞増殖がん N-myc ras

项目摘要

Although most types of cells require attachment to the substrate for proliferation, tumor cells do proliferate without attachment to the substrate, which is called as anchorage independent growth. Studies of tumorigenesis lead to understand anchorage independent growth, from which a new aspect for cell proliferation itself will emerge. Transformation of normal cells usually requires two or more cooperative oncogenic events. However, the mechanism of the oncogenic cooperation is unclear. The combination of c-myc and activated ras is the first pair of characterized genes to show oncogenic cooperation. First, in this project, I isolated cells transformed by myc and activated ras in which c-Myc expression is controllable (J. Biochem. 1998). Next. I isolated a transformed cell line in which activation of c-Myc and Ras are independently controllable (Oncogene 2000). Using these cells I show that after establishment of the transformed state by c-myc and activated ras, suppression of Ras/MEK signaling initiates apoptosis that is dependent on c-Myc activity. These results suggest that one of the conditions required for establishment of the u-;1ilSformeLl state is a block of apoptosis involving MEK activity. Suppression of apoptosis by MEK is not critical in general, but in cells transformed by c-myc plus a gene that activates the MAPK cascade it is necessary to avoid cell death. Furthermore I found that apoptosis regulation mechanism shown here include a novel regulatory mechanism for myc-dependent apoptosis.

尽管大多数类型的细胞需要附着于基质以进行增殖，但肿瘤细胞确实在不附着于基质的情况下增殖，这被称为锚定非依赖性生长。对肿瘤发生的研究有助于理解锚定非依赖性生长，从而为细胞增殖本身提供了一个新的视角。正常细胞的转化通常需要两个或多个协同致癌事件。然而，致癌合作的机制尚不清楚。c-myc和激活的ras的组合是第一对显示致癌合作的特征基因。首先，在这个项目中，我分离了由myc和激活的ras转化的细胞，其中c-Myc表达是可控的（J.Biochem.1998）。下一个我分离了一个转化的细胞系，其中c-Myc和Ras的激活是独立可控的（Oncogene 2000）。使用这些细胞，我表明，建立后的转化状态的c-myc和激活的Ras，Ras/MEK信号的抑制启动依赖于c-Myc活性的细胞凋亡。这些结果表明，建立u-11 Sformel状态所需的条件之一是阻断涉及MEK活性的细胞凋亡。一般来说，MEK抑制细胞凋亡并不重要，但在由c-myc加上激活MAPK级联反应的基因转化的细胞中，有必要避免细胞死亡。此外，我还发现，本文所展示的细胞凋亡调控机制包括一种新的myc依赖的细胞凋亡调控机制。