v-Src generates a p53-independent apoptotic signal.
v-Src generates a p53-independent apoptotic signal.
复制标题
v-Src 产生独立于 p53 的细胞凋亡信号。
DOI：
10.1128/mcb.20.24.9271-9280.2000
复制
发表时间：
2000
影响因子：
5.3
通讯作者：
Martin,GS
中科院分区：
文献类型：
--
作者：
Webb,BL;Jimenez,E;Martin,GS
凋亡的逃避似乎是肿瘤进展中的必要事件。一些癌基因，如c-mycand E1 A，在缺乏生存因子的情况下诱导细胞凋亡。然而，其他的，如bcl-2和v-src，激活抗凋亡通路。对于v-Src，这些抗凋亡途径依赖于Ras、磷脂酰肌醇（PI）3-激酶和Stat 3的功能。在这里，我们问是否v-Src可以激活一个促凋亡信号时，生存信号被抑制。我们发现，当Ras和PI 3-激酶的功能被抑制时，V-src转化的大鼠2成纤维细胞发生凋亡，表现为粘附性丧失、核碎裂和染色体DNA降解。凋亡反应依赖于caspase 3的激活。在类似的条件下，非转化的Rat-2细胞经历相当低水平的凋亡。v-Src诱导的细胞凋亡伴随线粒体膜电位的降低和细胞色素的释放，并被bcl-2的过表达所阻断，表明它是由线粒体途径介导的。然而，v-Src诱导的细胞凋亡不伴随p53水平的增加，并且不依赖于p53功能。因此，v-Src产生p53非依赖性促凋亡信号。
Evasion of apoptosis appears to be a necessary event in tumor progression. Some oncogenes, such asc-mycand E1A, induce apoptosis in the absence of survival factors. However, others, such asbcl-2and v-src, activate antiapoptotic pathways. For v-Src, these antiapoptotic pathways are dependent on the function of Ras, phosphatidylinositol (PI) 3-kinase, and Stat3. Here we asked whether v-Src can activate a proapoptotic signal when survival signaling is inhibited. We show that when the functions of Ras and PI 3-kinase are inhibited, v-src-transformed Rat-2 fibroblasts undergo apoptosis, evidenced by loss of adherence, nuclear fragmentation, and chromosomal DNA degradation. The apoptotic response is dependent on activation of caspase 3. Under similar conditions nontransformed Rat-2 cells undergo considerably lower levels of apoptosis. Apoptosis induced by v-Src is accompanied by a loss of mitochondrial membrane potential and release of cytochromecand is blocked by overexpression ofbcl-2, indicating that it is mediated by the mitochondrial pathway. However apoptosis induced by v-Src is not accompanied by an increase in the level of p53 and is not dependent on p53 function. Thus v-Src generates a p53-independent proapoptotic signal.