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转染并表达c-myc原癌基因后人类小细胞肺癌细胞系的表型变化。

Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

作者信息

Johnson B E, Battey J, Linnoila I, Becker K L, Makuch R W, Snider R H, Carney D N, Minna J D

出版信息

J Clin Invest. 1986 Aug;78(2):525-32. doi: 10.1172/JCI112604.

DOI:10.1172/JCI112604
PMID:3016030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC423589/
Abstract

Small cell lung cancer growing in cell culture possesses biologic properties that allow classification into two categories: classic and variant. Compared with classic small cell lung cancer cell lines, variant lines have altered large cell morphology, shorter doubling times, higher cloning efficiencies in soft agarose, and very low levels of L dopa decarboxylase production and bombesin-like immunoreactivity. C-myc is amplified and expressed in some small cell lung cancer cell lines and all c-myc amplified lines studied to date display the variant phenotype. To investigate if c-myc amplification and expression is responsible for the variant phenotype, a normal human c-myc gene was transfected into a cloned classic small cell lung cancer cell line not amplified for or expressing detectable c-myc messenger RNA (mRNA). Clones were isolated with one to six copies of c-myc stably integrated into DNA that expressed c-myc mRNA. In addition, one clone with an integrated neo gene but a deleted c-myc gene was isolated and in this case c-myc was not expressed. C-myc expression in transfected clones was associated with altered large cell morphology, a shorter doubling time, and increased cloning efficiency, but no difference in L dopa decarboxylase levels and bombesin-like immunoreactivity. We conclude increased c-myc expression observed here in transfected clones correlates with some of the phenotypic properties distinguishing c-myc amplified variants from unamplified classic small cell lung cancer lines.

摘要

在细胞培养中生长的小细胞肺癌具有一些生物学特性,可分为两类:经典型和变异型。与经典小细胞肺癌细胞系相比,变异型细胞系具有改变的大细胞形态、更短的倍增时间、在软琼脂糖中更高的克隆效率,以及极低水平的L-多巴脱羧酶产生和蛙皮素样免疫反应性。C-myc在一些小细胞肺癌细胞系中被扩增和表达,并且迄今为止研究的所有C-myc扩增细胞系均表现出变异型表型。为了研究C-myc扩增和表达是否导致变异型表型,将一个正常的人类C-myc基因转染到一个克隆的经典小细胞肺癌细胞系中,该细胞系未扩增或不表达可检测到的C-myc信使核糖核酸(mRNA)。分离出稳定整合有1至6个拷贝C-myc且表达C-myc mRNA的DNA的克隆。此外,分离出一个整合有新霉素基因但缺失C-myc基因的克隆,在这种情况下C-myc不表达。转染克隆中的C-myc表达与改变的大细胞形态、更短的倍增时间和增加的克隆效率相关,但L-多巴脱羧酶水平和蛙皮素样免疫反应性没有差异。我们得出结论,在此观察到的转染克隆中C-myc表达增加与区分C-myc扩增变异型与未扩增经典小细胞肺癌细胞系的一些表型特性相关。

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