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原癌基因met和肝细胞生长因子基因的致瘤性。

Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.

作者信息

Rong S, Bodescot M, Blair D, Dunn J, Nakamura T, Mizuno K, Park M, Chan A, Aaronson S, Vande Woude G F

机构信息

ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702.

出版信息

Mol Cell Biol. 1992 Nov;12(11):5152-8. doi: 10.1128/mcb.12.11.5152-5158.1992.

DOI:10.1128/mcb.12.11.5152-5158.1992
PMID:1406687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC360449/
Abstract

The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice.

摘要

原癌基因met是肝细胞生长因子/分散因子(HGF/SF)的酪氨酸激酶生长因子受体。先前的研究表明,与致癌性tpr-met一样,小鼠原癌基因met可转化NIH 3T3细胞。我们已经建立了稳定表达人(Methu)和小鼠(Metmu)原癌基因met产物的NIH 3T3细胞系。蛋白质产物经过适当加工并出现在细胞表面。NIH 3T3细胞表达内源性小鼠HGF/SF mRNA,提示Metmu介导的转化存在自分泌激活机制。然而,与Metmu相比,Methu在NIH 3T3细胞中的致瘤活性非常低,但当Methu和HGF/SFhu共表达时,可有效发生肿瘤形成。这些结果与自分泌转化机制一致,并进一步表明内源性鼠源因子不能有效激活Methu的致瘤潜能。交换外部配体结合域的人源和鼠源相互嵌合受体所观察到的致瘤性支持了这一结论。我们还表明,在NIH 3T3细胞中表达的HGF/SFhu可在裸鼠中产生肿瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/2d462d2d944f/molcellb00134-0358-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/89ba97f2c391/molcellb00134-0356-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/d67719750186/molcellb00134-0357-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/3b923a16d5c6/molcellb00134-0357-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/2d462d2d944f/molcellb00134-0358-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/89ba97f2c391/molcellb00134-0356-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/d67719750186/molcellb00134-0357-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/3b923a16d5c6/molcellb00134-0357-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ca/360449/2d462d2d944f/molcellb00134-0358-a.jpg

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本文引用的文献

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Molecular cloning of a new transforming gene from a chemically transformed human cell line.从化学转化的人细胞系中克隆一个新的转化基因
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