Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma.
Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma.
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c-raf-1 和 c-myc 表达对人小细胞肺癌体外模型辐射反应的影响。
DOI：
10.1006/bbrc.1998.9660
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发表时间：
1998
影响因子：
3.1
通讯作者：
Kasid,U
中科院分区：
文献类型：
--
作者：
Pfeifer,A;Mark,G;Leung,S;Dougherty,M;Spillare,E;Kasid,U
在本研究中，我们检测了用c-raf-1和/或c-myc.稳定转染的猴病毒40大肿瘤抗原永活人支气管上皮细胞（BEAS-2B）的辐射存活反应，与c-myc（2B-myc）或对照载体转染（2B-neo） （2B-raf,D0= 2.445 Gy; 2B-raf/myc,D0= 2.46 Gy; 2B-myc,D0= 1.501 Gy; 2B-neo, D0= 2.029 Gy）相比，c-raf-1和c-raf- 2双转染（2B-raf/myc,D0= 2.46 Gy）相对耐辐射。超氧化物歧化酶（SOD） mRNA的稳态水平在辐射耐药细胞（2B-raf和2B-raf/myc）中较高。此外，2B-raf/mycor转染的2B-myc在细胞周期的G2+M期的细胞数量相对较高，而不是2B-raf/mycor。这些发现提供了实验证据，表明Raf-1的表达与2B-raf/ myctran侵染物对2B-raf/ myctran侵染物的辐射抗性反应相关，并提示SOD在Raf-1相关的辐射抗性中起作用。由于2B-raf转染剂无致瘤性，而双转染剂（2B-raf/myc）具有致瘤性，并且在小细胞肺癌中发现了一些表型特征，因此我们的数据暗示了raf -1介导的辐射保护机制与肺肿瘤进展之间的分离。
In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-1 and/or c-myc.C-raf-1 transfectants (2B-raf), and c-raf-1andc-mycdouble transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc(2B-myc) or control vector transfectants (2B-neo) (2B-raf,D0= 2.445 Gy; 2B-raf/myc,D0= 2.46 Gy; 2B-myc,D0= 1.501 Gy; 2B-neo, D0= 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-rafand 2B-raf/myc). In addition, 2B-rafbut not 2B-raf/mycor 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-1 expression correlates with the radiation-resistant response of 2B-rafor 2B-raf/myctransfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raftransfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-1-mediated mechanisms of radiation protection and progression of lung neoplasia.