TY - JOUR
T1 - Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells
AU - Di Fiore, Pier Paolo
AU - Pierce, Jacalyn H.
AU - Fleming, Timothy P.
AU - Hazan, Rachel
AU - Ullrich, Axel
AU - King, C. Richter
AU - Schlessinger, Joseph
AU - Aaronson, Stuart A.
PY - 1987/12/24
Y1 - 1987/12/24
N2 - The epidermal growth factor receptor (EGFR) gene is frequently amplified and/or overexpressed in human malignancies. To investigate the biological effects of its overexpression, we constructed a eukaryotic vector containing human EGFR cDNA. Introduction of this construct led to reconstitution of functional EGF receptors in NR6 mutant cells, which are normally devoid of this receptor. Transfection of NIH 3T3 resulted in no significant alterations in growth properties. However, EGF addition led to the formation of densely growing transformed foci in liquid culture and colonies in semisolid medium. NIH 3T3-EGFR clonal lines, which expressed the EGF at 500- to 1000-fold levels over control NIH 3T3 cells, demonstrated a marked increase in DNA synthesis in response to EGF. Thus EGF receptor overexpression appears to amplify normal EGF signal transduction. Finally, high levels of EGFR expression, which conferred a transformed phenotype to NIH 3T3 cells in the presence of ligand, were demonstrated in representative human tumor cell lines that contained amplified copies of the EGFR gene.
AB - The epidermal growth factor receptor (EGFR) gene is frequently amplified and/or overexpressed in human malignancies. To investigate the biological effects of its overexpression, we constructed a eukaryotic vector containing human EGFR cDNA. Introduction of this construct led to reconstitution of functional EGF receptors in NR6 mutant cells, which are normally devoid of this receptor. Transfection of NIH 3T3 resulted in no significant alterations in growth properties. However, EGF addition led to the formation of densely growing transformed foci in liquid culture and colonies in semisolid medium. NIH 3T3-EGFR clonal lines, which expressed the EGF at 500- to 1000-fold levels over control NIH 3T3 cells, demonstrated a marked increase in DNA synthesis in response to EGF. Thus EGF receptor overexpression appears to amplify normal EGF signal transduction. Finally, high levels of EGFR expression, which conferred a transformed phenotype to NIH 3T3 cells in the presence of ligand, were demonstrated in representative human tumor cell lines that contained amplified copies of the EGFR gene.
UR - http://www.scopus.com/inward/record.url?scp=0023663896&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023663896&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(87)90592-7
DO - 10.1016/0092-8674(87)90592-7
M3 - Article
C2 - 3500791
AN - SCOPUS:0023663896
SN - 0092-8674
VL - 51
SP - 1063
EP - 1070
JO - Cell
JF - Cell
IS - 6
ER -