PMID- 8036013 OWN - NLM STAT- MEDLINE DCOM- 19940815 LR - 20181130 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 9 IP - 8 DP - 1994 Aug TI - Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. PG - 2313-20 AB - The most common type of alteration of the epidermal growth factor receptor gene (EGFR) in human glioblastomas results in the synthesis of an aberrant mRNA lacking 801 bases that encode amino acids 6-273 of the receptor's extracellular domain. To study the effects of this mutation on receptor function, we have developed chinese hamster ovary cell transfectants which express the mutant EGF receptor. Comparison of wild-type and mutant receptor properties in this cell host indicates that the truncated receptor does not bind EGF or TGF-alpha and, consequently, DNA synthesis is not stimulated in cultures of mutant transfectants by either grown factor. However, levels of DNA synthesis determined for mutant transfectants in serum-free media are several-fold higher than those determined for corresponding cultures of wild-type transfectants. Western blot analysis with anti-phosphotyrosine antibody indicates that the mutant receptor is constitutively phosphorylated in CHO cells, and the same analysis applied to lysates of glioblastoma biopsies reveals the altered receptor is readily detectable as a phosphotyrosine protein in tumors for which there is evidence of corresponding EGFR gene and transcript alterations. In total, these results indicate that the aberrant EGF receptor synthesized in glioblastomas, and which lacks a portion of the extracellular domain necessary for ligand binding, is an activated tyrosine kinase. FAU - Ekstrand, A J AU - Ekstrand AJ AD - Department of Neurosurgery, Emory University SOM, Atlanta, Georgia 30322. FAU - Longo, N AU - Longo N FAU - Hamid, M L AU - Hamid ML FAU - Olson, J J AU - Olson JJ FAU - Liu, L AU - Liu L FAU - Collins, V P AU - Collins VP FAU - James, C D AU - James CD LA - eng GR - CA55728/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - CHO Cells MH - Cricetinae MH - ErbB Receptors/chemistry/genetics/*physiology MH - Glioblastoma/*genetics MH - Humans MH - *Polymerase Chain Reaction MH - Signal Transduction MH - Transfection EDAT- 1994/08/01 00:00 MHDA- 1994/08/01 00:01 CRDT- 1994/08/01 00:00 PHST- 1994/08/01 00:00 [pubmed] PHST- 1994/08/01 00:01 [medline] PHST- 1994/08/01 00:00 [entrez] PST - ppublish SO - Oncogene. 1994 Aug;9(8):2313-20.