Post-transcriptional deregulation of myc genes in lung cancer cell lines
Post-transcriptional deregulation of myc genes in lung cancer cell lines
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DOI：
10.1165/ajrcmb.23.4.4233
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发表时间：
2000-10-01
影响因子：
6.4
通讯作者：
Laird-Offringa, IA
中科院分区：
文献类型：
--
作者：
Bernasconi, NL;Wormhoudt, TAM;Laird-Offringa, IA
Myc家族的基因在肺癌中经常过度表达。基因扩增可以解释部分肿瘤和细胞系中这些基因的失控，但在大多数情况下，myc表达升高的原因尚不清楚。我们研究了信使RNA(MRNA)的稳定性是否可能有助于肺癌细胞系中myc基因的过度表达。分析了11个细胞系和永生化人胚肺细胞中c-myc或N-myc mRNA的衰变模式。8株肺癌细胞株c-myc或N-myc转录本稳定。为了确定这种稳定是否是myc基因所独有的，我们还研究了不稳定的c-fos原癌基因mRNA的衰变模式。表现出myc mRNA稳定的同一细胞系显示c-fos信息异常缓慢的衰减，这表明c-fos和myc转录本的异常衰减之间可能存在相关性。相反，以细胞周期特异性方式降解的组蛋白2B mRNA的半衰期似乎与myc和fos的半衰期无关。我们的结果表明，在肺癌中，负责破坏不稳定原癌基因mRNAs的mRNA衰变途径可能普遍受到影响。
Genes of the myc family are frequently overexpressed in lung cancer. Gene amplification can explain the deregulation of these genes in a subset of tumors and cell lines, but in most cases, the cause of the elevated myc expression remains unknown. We examined whether messenger RNA (mRNA) stabilization could be contributing to myc gene overexpression in lung cancer cell lines. The decay pattern of c-myc or N-myc mRNA was analyzed in 11 such cell lines and in unimmortalized human embryonic lung cells. Eight lung cancer cell lines showed stabilization of c-myc or N-myc transcripts. To determine whether this stabilization was unique to myc genes, the decay pattern of the unstable c-fos proto-oncogene mRNA was also studied. The same cell lines that exhibited stabilization of myc mRNA showed an abnormally slow decay of the c-fos message, suggesting that there might be a correlation between the abnormal decay of c-fos and myc transcripts. In contrast, the half-life of histone 2B mRNA, which is degraded in a cell cycle-specific manner, did not appear to correlate with that of myc and fos. Our results suggest that an mRNA decay pathway responsible for the destruction of unstable proto-oncogene mRNAs may be commonly affected in lung cancers.