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表皮生长因子受体相关原癌基因erbB-2在人乳腺肿瘤细胞系中通过不同分子机制实现过表达。

Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms.

作者信息

Kraus M H, Popescu N C, Amsbaugh S C, King C R

出版信息

EMBO J. 1987 Mar;6(3):605-10. doi: 10.1002/j.1460-2075.1987.tb04797.x.

DOI:10.1002/j.1460-2075.1987.tb04797.x
PMID:3034598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC553440/
Abstract

Amplification of the erbB/EGF receptor and a structurally related gene, designated erbB-2, have previously been detected in a variety of human tumors. In a series of human mammary tumor cell lines, analysis of transcripts of these genes revealed elevated levels of one or the other in more than 60% of tumors analyzed. Eight cell lines demonstrated erbB-2 mRNA levels ranging from 4- to 128-fold above those of normal controls. erbB-2 expression was evaluated in comparison to the expression level of actin observed in these cell lines. There was no evidence of an aberrantly sized erbB-2 transcript in any of these lines. Immunoblot analysis indicated elevation in levels of the 185-kd product of the erbB-2 gene expressed by these cells. In four lines erbB-2 gene amplification in the absence of an apparent gene rearrangement was demonstrated. In a representative cell line of this type, SK-BR-3, the amplified erbB-2 gene copies were located in an aberrant chromosomal location. Four additional cell lines, which demonstrated 4- to 8-fold overexpression of erbB-2 mRNA, did not exhibit gene amplification. In a representative cell line of this type ZR-75-1, an apparently normal chromosomal location was found for the erbB-2 gene. Our findings indicate that overexpression of the erbB-2 gene in mammary tumor cell lines is frequent and associated with different genetic abnormalities.

摘要

先前已在多种人类肿瘤中检测到erbB/EGF受体及一个结构相关基因(命名为erbB - 2)的扩增。在一系列人类乳腺肿瘤细胞系中,对这些基因转录本的分析显示,在超过60%的被分析肿瘤中,其中一种基因的水平有所升高。八个细胞系的erbB - 2 mRNA水平比正常对照高4至128倍。与这些细胞系中观察到的肌动蛋白表达水平相比,对erbB - 2表达进行了评估。在这些细胞系中均未发现大小异常的erbB - 2转录本。免疫印迹分析表明,这些细胞表达的erbB - 2基因的185 - kd产物水平升高。在四个细胞系中,证实存在erbB - 2基因扩增但无明显的基因重排。在这种类型的一个代表性细胞系SK - BR - 3中,扩增的erbB - 2基因拷贝位于异常的染色体位置。另外四个细胞系的erbB - 2 mRNA过表达4至8倍,但未表现出基因扩增。在这种类型的一个代表性细胞系ZR - 75 - 1中,发现erbB - 2基因位于明显正常的染色体位置。我们的研究结果表明,erbB - 2基因在乳腺肿瘤细胞系中的过表达很常见,并且与不同的基因异常有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/7b5367fc0143/emboj00243-0065-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/5cb6191f4233/emboj00243-0063-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/56e25d07b867/emboj00243-0064-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/98afa80a6f49/emboj00243-0064-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/7b5367fc0143/emboj00243-0065-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/5cb6191f4233/emboj00243-0063-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/56e25d07b867/emboj00243-0064-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/98afa80a6f49/emboj00243-0064-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dda/553440/7b5367fc0143/emboj00243-0065-a.jpg

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