Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts.
The protein product of the rodent neu oncogene, p185neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c-erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c-neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c-neu. During efforts to characterize the interaction of p185c-neu with EGFR further, we created cell lines that simultaneously overexpress both p185c-neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.
Kokai
Y
Y
Department of Pathology, University of Pennsylvania, Philadelphia 19104-6082.
Myers
J N
JN
Wada
T
T
Brown
V I
VI
LeVea
C M
CM
Davis
J G
JG
Dobashi
K
K
Greene
M I
MI
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D051379:Mice; D008819:Mice, Nude; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases