COEXPRESSION PATTERN OF C-MYC ASSOCIATED GENES IN A SMALL-CELL LUNG-CANCER CELL-LINE WITH HIGH STEADY-STATE C-MYC TRANSCRIPTION
COEXPRESSION PATTERN OF C-MYC ASSOCIATED GENES IN A SMALL-CELL LUNG-CANCER CELL-LINE WITH HIGH STEADY-STATE C-MYC TRANSCRIPTION
复制标题
DOI：
10.1006/bbrc.1995.2199
复制
发表时间：
1995-08-24
影响因子：
3.1
通讯作者：
WELTER, C
中科院分区：
文献类型：
--
作者：
DOOLEY, S;WUNDRACK, I;WELTER, C
c-Myc 蛋白参与细胞转化和有丝分裂发生，但也可作为分化和程序性细胞死亡的有效诱导剂。 Max 作为 Myc 的专性异二聚体伴侣，介导其作为特定转录激活剂和转化蛋白的功能。 Mad 和 Mxi1 蛋白均与 Max 异二聚化，并相互竞争有限数量的 Max。 Myc 的转录激活可以通过增加 Mad 或 Mxi1 的量来抑制。本报告显示了小细胞肺癌 (SCLC) 细胞系 (GLC4) 中这些 Myc 相关因子在 mRNA 水平的表达模式，其特征是 c-myc 扩增和强组成型 c-myc 过表达。我们发现这些基因具有转录活性，但不受高 c-myc 转录的影响。 Max 在细胞周期进展过程中持续以相对较低的水平转录。 Mad 和 mxi1 mRNA 在增殖细胞中的水平出人意料地高。在细胞血清饥饿期间，Mad 进一步上调，mxil 下调至基础水平。我们进一步分析了 c-fos、c-jun、c-myb 和 nm23 的活性，据描述它们参与 c-myc 转录激活。 c-jun 和 c-fos 没有被组成型激活，可以排除作为调节剂。相反，高稳态c-myc影响这两个基因的血清刺激瞬时激活机制。我们鉴定了高拷贝数 nm23 mRNA，其作为假定的 c-myc 转录激活剂的作用正在研究中。我们的结果表明，c-myc 的组成型过表达不需要所测试的核癌基因的活性，并且功能相关蛋白的 mRNA 表达模式不受影响。 (C) 1995 年学术出版社有限公司。
The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxil was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation. c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced. (C) 1995 Academic Press, lnc.