AMPLIFICATION AND EXPRESSION OF THE C-MYC ONCOGENE IN HUMAN-LUNG CANCER CELL-LINES
AMPLIFICATION AND EXPRESSION OF THE C-MYC ONCOGENE IN HUMAN-LUNG CANCER CELL-LINES
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DOI：
10.1038/306194a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
MINNA, JD
中科院分区：
文献类型：
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作者：
LITTLE, CD;NAU, MM;MINNA, JD
在人类肿瘤中观察到涉及c-myconcogene的遗传变化。特别是，c-mycgene在伯基特淋巴瘤中易位1 - 3，并在人早幼粒细胞白血病细胞系中扩增。HL-60，含有双微小染色体（DM）4，5。最近，扩增的c-mycgene已被定位在具有神经内分泌特性的人结肠癌细胞系科洛320中的染色体均质染色区域（HSR）上6。此外，c-mycis在一些人类肿瘤细胞系中表达量增加，在某些情况下，人类小细胞肺癌（SCLC）含有DM和HSR 7，8。这些发现促使我们研究c-mycgene及其RNA在一系列人肺癌细胞系中的表达。我们现在报告的扩增和表达的c-myconcogene在系统以外的B细胞淋巴瘤9，即人肺癌。在18株人肺癌细胞系中，有8株在EcoR Ⅰ c-mycDNA上扩增出12.5kb的条带。特别令人感兴趣的是具有高度c-mycDNA扩增（20-76倍）和大大增加的c-mycRNA水平的5个SCLC系。所有五个细胞系都属于SCLC的变异类型（SCLC-V），其特征在于形态改变、缺乏某些SCLC分化功能的表达以及比纯SCLC更恶性的行为10，11。已经核型分析的五个品系中的三个也含有DM或HSR。在所有SCLC-V类细胞系中发现一个大大扩增的c-mycgene，这强烈表明c-mycgene在人肺癌的表型转化和恶性行为中的作用。
Genetic changes involving the c-myconcogene have been observed in human tumours. In particular, the c-mycgene is translocated in Burkitt's lymphoma1–3and is amplified in the human promyelocytic leukaemia cell line. HL-60, which contains double minute chromosomes (DMs)4,5. More recently, an amplified c-mycgene has been positioned on a chromosomal homogeneous staining region (HSR) in a human colon cancer cell line, COLO 320, with neuroendocrine properties6. Furthermore, c-mycis expressed in increased amounts in some human tumour lines, and in some cases, human small cell lung cancers (SCLC) contain DMs and HSRs7,8. These findings prompted us to study the c-mycgene and its RNA expression in a series of human lung cancer cell lines. We now report amplification and expression of the c-myconcogene in a system other than B-cell lymphomas9, namely human lung cancer. Of 18 human lung cancer cell lines tested, 8 showed an amplified 12.5-kilobase (kb)EcoRI c-mycDNA band. Of particular interest are five SCLC lines with a high degree of c-mycDNA amplification (20–76-fold) and greatly increased levels of c-mycRNA. All five lines reside in the variant class of SCLC (SCLC-V) characterized by altered morphology, lack of expression of some SCLC-dlfferentlated functions and more malignant behaviour than pure SCLC10,11. Three of the five lines which have been karyotyped also contain DMs or HSRs. The finding of a greatly amplified c-mycgene in all cell lines of the SCLC-V class examined strongly suggests a role for the c-mycgene in the phenotypic conversion and malignant behaviour of human lung cancer.