Elevated expression of the junB proto-oncogene is essential for v-fos induced transformation of Rat-1 cells.
Elevated expression of the junB proto-oncogene is essential for v-fos induced transformation of Rat-1 cells.
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发表时间：
1994-10
期刊：
影响因子：
8
通讯作者：
J. V. Van Amsterdam;Y. Wang;R. Sullivan;H. Zarbl
中科院分区：
文献类型：
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作者：
J. V. Van Amsterdam;Y. Wang;R. Sullivan;H. Zarbl
我们之前描述了从v-fos转化的鼠-1细胞诱变群体中分离非致瘤性回调物（Zarbl等，1987）。在本研究中，我们研究了逆转表型是由改变c-jun或junB原癌基因表达或活性的突变引起的可能性。结果表明，与转化的亲本细胞相比，c-jun mRNA和蛋白的水平在回归细胞中没有变化，并且c-jun的异位过表达未能使回归细胞重新转化。虽然在反向的EMS-1-19中检测到一个突变等位基因，但该突变等位基因的过表达未能抑制v-fos诱导的细胞转化。这些结果表明，逆转表型不是由c-jun基因的表达改变或突变引起的。与c-jun的结果相反，在相关的EMS-1-19中，junB mRNA和蛋白的水平降低了两到三倍。junB的异位过表达诱导了逆向EMS-1-19的转化，但未能转化大鼠1细胞。此外，用表达反义junB mRNA的载体转染的v-fos转化细胞中约有10%获得了非转化表型。这些结果表明，junB的表达高于阈值水平对于v-fos诱导的大鼠-1成纤维细胞转化至关重要。
We previously described the isolation of non-tumorigenic revertants from mutagenized populations of v-fos-transformed Rat-1 cells (Zarbl et al., 1987). In the present study we examined the possibility that the revertant phenotype resulted from mutations that altered the expression or activities of the c-jun or junB proto-oncogenes. The results demonstrated that levels of the c-jun mRNA and protein were unchanged in the revertants when compared to the transformed parental cells, and ectopic overexpression of c-jun failed to retransform the revertants. Although one mutant allele was detected in revertant EMS-1-19, overexpression of this mutant allele failed to inhibit v-fos induced cell transformation. Together these results indicated that the revertant phenotype did not result from altered expression or mutations in the c-jun gene. In contrast to the results obtained with c-jun, the levels of junB mRNA and protein were found to be reduced two- or threefold in revertant EMS-1-19. Ectopic overexpression of junB induced transformation of revertant EMS-1-19, but failed to transform Rat-1 cells. Moreover, about 10% of v-fos transformed cells transfected with vectors that express antisense junB mRNA acquired a non-transformed phenotype. Together these results indicate that expression of junB above a threshold level is essential for v-fos-induced transformation of Rat-1 fibroblasts.