Characterization of c-myc-transformed rat fibroblasts resistant to apoptosis induced ny growth factor deprivation.
Characterization of c-myc-transformed rat fibroblasts resistant to apoptosis induced ny growth factor deprivation.
复制标题
c-myc 转化的大鼠成纤维细胞抵抗细胞凋亡诱导的 ny 生长因子剥夺的特征。
DOI：
10.1006/excr.1996.0110
复制
发表时间：
1996
影响因子：
3.7
通讯作者：
Small,MB
中科院分区：
文献类型：
--
作者：
Dhanaraj,SN;Marcus,AM;Korah,RM;Iwata,K;Small,MB
在适当的条件下（例如，停止生长因子），c-mycin啮齿动物成纤维细胞的表达失调导致大量细胞凋亡。为了更好地理解这一过程，我们选择了对生长因子剥夺诱导的细胞死亡具有抗性的c-myc转化的Rat1A成纤维细胞。一个克隆分离物在无血清培养基中表现出较长的存活时间，并显示出与细胞凋亡相关的DNA片段化水平降低。这些细胞也抵抗蛋白激酶抑制剂staurosporine诱导的凋亡。他们保留了转化的细胞表型，并以不变的方式表达了原病毒人类c-mycallele，这强烈表明除了c- mycaller外，细胞基因的突变导致了抗凋亡表型。该细胞系的体细胞杂交分析结果与隐性突变一致。我们的发现提示了肿瘤细胞凋亡的一种新机制，并为研究其在肿瘤发生和抗肿瘤治疗中的作用提供了一个模型系统。
Under appropriate conditions (e.g., growth factor withdrawal), the deregulated expression of c-mycin rodent fibroblasts leads to substantial cell death due to apoptosis. To better understand this process, we selected for c-myc-transformed Rat1A fibroblasts that were resistant to growth factor deprivation-induced cell death. One clonal isolate exhibited prolonged survival in serum-free medium and displayed reduced levels of apoptosis-related DNA fragmentation. These cells were also resistant to induction of apoptosis by the protein kinase inhibitor staurosporine. They retained a transformed cell phenotype and expressed the proviral human c-mycallele in an unaltered fashion, strongly indicating that the mutation of a cellular gene other than c-mycaccounts for the apoptosis-resistant phenotype. The results of somatic cell hybrid analysis of this cell line are consistent with a recessive mutation. Our findings suggest a novel mechanism for abrogation of apoptosis in neoplastic cells and provide a model system for the study of its role in tumorigenesis and resistance to antineoplastic therapy.