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人胶质瘤异种移植中表皮生长因子受体基因的扩增与表达

Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts.

作者信息

Humphrey P A, Wong A J, Vogelstein B, Friedman H S, Werner M H, Bigner D D, Bigner S H

机构信息

Brain Tumor Research [D.D.B., M.H.W.] and Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

Cancer Res. 1988 Apr 15;48(8):2231-8.

PMID:3258189
Abstract

Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene. Tissue identity between biopsy and xenografts was confirmed by karyotypic profiles, which showed that each glioma xenograft retained structural abnormalities, including double minute chromosomes, present in the parent glioma. EGFR gene amplification was found in six of the eight glioma biopsies and their corresponding xenografts. Expression of the EGFR gene was measured by Scatchard analysis, affinity reactions, immunoprecipitations, Western immunoblots, and immunocytochemistry; significant expression of the EGFR gene was only detectable in xenografts with EGFR gene amplification. Moreover, five of the six xenografts with EGFR gene amplification demonstrated structural alterations of the EGFR gene, which was associated with low-molecular-weight EGFR proteins. These xenografts represent an excellent tissue source and in vivo model system for characterizing the epidermal growth factor receptor in malignant human gliomas.

摘要

将来自8例恶性人脑胶质瘤的异种移植物接种于无胸腺小鼠体内,用于研究表皮生长因子受体(EGFR)基因的扩增和表达。通过核型分析证实活检组织与异种移植物之间的组织一致性,结果显示每个胶质瘤异种移植物均保留了亲代胶质瘤中存在的结构异常,包括双微体染色体。在8例胶质瘤活检组织及其相应的异种移植物中,有6例发现EGFR基因扩增。通过Scatchard分析、亲和反应、免疫沉淀、Western免疫印迹和免疫细胞化学检测EGFR基因的表达;仅在EGFR基因扩增的异种移植物中可检测到EGFR基因的显著表达。此外,6例EGFR基因扩增的异种移植物中有5例显示EGFR基因的结构改变,这与低分子量EGFR蛋白有关。这些异种移植物是用于表征恶性人脑胶质瘤中表皮生长因子受体的优良组织来源和体内模型系统。

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