Fleming T P, Saxena A, Clark W C, Robertson J T, Oldfield E H, Aaronson S A, Ali I U
Laboratory of Cellular and Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1992 Aug 15;52(16):4550-3.
Analysis of genomic organization and expression of platelet-derived growth factor receptors (PDGFR) and epidermal growth factor receptor (EGFR) in human malignant gliomas showed amplification and overexpression of both receptors in distinct subsets of tumors. Amplification of the alpha PDGFR was detected in 4 of 50 glioblastomas (8%). EGFR was amplified in 9 of the 50 tumors (18%). Western blot analysis showed elevated expression of alpha PDGFR and EGFR proteins in 4 (24%) and 3 (18%), respectively, of 17 tumor specimens analyzed. Increased production of alpha PDGFR as well as EGFR proteins was observed in the presence or absence of gene amplification. Three of the 4 tumors with elevated levels of alpha PDGFR also overexpressed the beta PDGFR, which was present as a single copy gene in all 50 tumors analyzed. Our findings suggest that the amplification and/or overexpression either of EGFR or of the alpha PDGFR along with the coordinate overexpression of the beta PDGFR can contribute to the malignant phenotype of distinct subsets of human glioblastoma.
对人类恶性胶质瘤中血小板衍生生长因子受体(PDGFR)和表皮生长因子受体(EGFR)的基因组组织和表达分析显示,在不同的肿瘤亚群中这两种受体均有扩增和过表达。在50例胶质母细胞瘤中有4例(8%)检测到α-PDGFR扩增。50例肿瘤中有9例(18%)检测到EGFR扩增。蛋白质印迹分析显示,在分析的17例肿瘤标本中,分别有4例(24%)和3例(18%)的α-PDGFR和EGFR蛋白表达升高。无论有无基因扩增,均观察到α-PDGFR以及EGFR蛋白产生增加。4例α-PDGFR水平升高的肿瘤中有3例也过表达β-PDGFR,在所有分析的50例肿瘤中β-PDGFR均以单拷贝基因形式存在。我们的研究结果表明,EGFR或α-PDGFR的扩增和/或过表达以及β-PDGFR的协同过表达可能促成了人类胶质母细胞瘤不同亚群的恶性表型。