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人类非小细胞肺癌细胞系中细胞癌基因的不同表达模式。

Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines.

作者信息

Kiefer P E, Wegmann B, Bacher M, Erbil C, Heidtmann H, Havemann K

机构信息

Philipps-University Marburg/Department of Internal Medicine, Federal Republic of Germany.

出版信息

J Cancer Res Clin Oncol. 1990;116(1):29-37. doi: 10.1007/BF01612637.

Abstract

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

摘要

在许多人类实体瘤中发现了细胞癌基因的改变和失调。除了少数几种始终表现出特定原癌基因改变的肿瘤类型外,大多数肿瘤与许多转录激活的细胞癌基因相关。在非小细胞肺癌(NSCLC)这一异质性肿瘤组中,关于原癌基因表达的特定模式尚无任何了解。因此,我们研究了一组细胞癌基因在NSCLC细胞系中的表达。从11个已建立的NSCLC细胞系(4个腺癌细胞系、3个鳞状细胞癌细胞系、3个大细胞癌细胞系和1个间皮瘤细胞系)中分离出DNA和RNA,并使用Southern、斑点印迹和Northern杂交技术进行分析。在所有NSCLC细胞系中均发现了c-myc RNA表达,L-myc仅在1个腺癌细胞系中表达,在所检测的11个细胞系中均未发现N-myc和c-myb表达。在DNA中未检测到c-myc扩增。在11个细胞系中的5个中观察到了v-sis相关mRNA,且与特定的NSCLC亚型无关。在所有测试细胞中均发现了v-src相关mRNA,与其他细胞系相比,在1个腺癌细胞系(A-549)中其水平有所升高。表皮生长因子(EGF)的结合位点先前已在NSCL中被描述,因此我们在所有NSCLC细胞系中均发现了编码EGF受体的erbB同源转录本。此外,在所有细胞系中均观察到了c-raf1、N-ras、Ki-ras和H-ras相关RNA表达。我们得出结论,L-myc、N-myc和c-myb在NSCLC中的表达频率低于在小细胞肺癌(SCLC)中的表达频率。同样,扩增似乎也不是NSCLC中c-myc原癌基因被激活的重要机制。在NSCLC细胞中未检测到癌基因表达的特定模式;每个检测的细胞系都显示出其自身的模式。然而,像erbB、ras、raf、src和c-myc这样的原癌基因的转录激活,它们都参与EGF的进展途径,可能是NSCLC的一个共同特征。

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