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人肝癌衍生细胞系中表皮生长因子受体的表达及生物合成变异

Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines.

作者信息

Carlin C R, Simon D, Mattison J, Knowles B B

机构信息

Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.

出版信息

Mol Cell Biol. 1988 Jan;8(1):25-34. doi: 10.1128/mcb.8.1.25-34.1988.

DOI:10.1128/mcb.8.1.25-34.1988
PMID:2827003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC363074/
Abstract

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

摘要

在六种人肝细胞癌衍生细胞系和一种人肝母细胞瘤衍生细胞系中分析了表皮生长因子（EGF）的表达情况，这些细胞系均保留了实质肝细胞的分化表型和功能。每个肝癌细胞系的受体表达水平与正常人成纤维细胞相似，约为每细胞10⁵个分子。然而，在体外异种移植肿瘤重建后获得的PLC/PRF/5细胞系的亚系NPLC/PRF/5，被发现每细胞表达4×10⁶个高亲和力EGF受体分子。在纳摩尔量配体存在的情况下，NPLC/PRF/5细胞系的增殖受到抑制。发现受体过表达是由于EGF受体基因扩增，而EGF受体编码序列无明显重排。虽然在肝癌细胞系中发现了EGF受体N-连接寡糖翻译后加工的细胞特异性差异，但未观察到PLC/PRF/5和NPLC/PRF/5受体之间的差异，也未检测到异常的受体相关物种。NPLC/PRF/5细胞系中的EGF受体基因扩增可能反映了基因组不稳定性以及在体内EGF浓度有限的情况下对具有增强生长潜力的变体的选择。从这个角度来看，EGF受体过表达可能代表了EGF反应性肝细胞中肿瘤进展的一种表现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/66cac36c0da3/molcellb00061-0054-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/45101c3fc044/molcellb00061-0051-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/54f4088c285f/molcellb00061-0052-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/316874b15e15/molcellb00061-0052-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/4ffd4bd347f0/molcellb00061-0052-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/c07bbfd377b4/molcellb00061-0052-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/4ac787383dda/molcellb00061-0053-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/477ef4845f01/molcellb00061-0053-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/66cac36c0da3/molcellb00061-0054-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/45101c3fc044/molcellb00061-0051-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/54f4088c285f/molcellb00061-0052-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/316874b15e15/molcellb00061-0052-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/4ffd4bd347f0/molcellb00061-0052-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/c07bbfd377b4/molcellb00061-0052-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/4ac787383dda/molcellb00061-0053-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/477ef4845f01/molcellb00061-0053-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e3/363074/66cac36c0da3/molcellb00061-0054-a.jpg

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