Premium
Interaction of the neu/p185 and EGF receptor tyrosine kinases: Implications for cellular transformation and tumor therapy
Author(s) -
Dougall William C.,
Qian Xiaolan,
Greene Mark I.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240530108
Subject(s) - epidermal growth factor , receptor tyrosine kinase , biology , receptor , growth factor receptor , cancer research , microbiology and biotechnology , tyrosine kinase , signal transduction , epidermal growth factor receptor , cell surface receptor , biochemistry
Growth factor receptors such as the epidermal growth factor receptor (EGFR) and the p185 c‐neu protein serve vital roles in the transduction of differentiation, developmental, or mitogenic signaling within normal cells. Two methods of analysis suggest that the inappropriately high expression of either protein tyrosine kinase promotes malignant transformation. First, data from in vitro experiments indicate that overexpression of either EGFR or p185 c‐neu (or the human homolog c‐erbB‐2) transforms cell‐lines. Second, analysis of primary tumors and tumor cell‐lines derived from many epithelial tissues (breast, stomach, ovary, and pancreas) show growth factor receptor gene amplification and elevated protein levels. The physical and functional interaction of p185 c‐neu and EGFR leads to the formation of a highly active, heterodimeric tyrosine kinase complex which synergistically activates cellular transformation. Anti‐receptor antibodies have shown potential utility for the down modulation of these cell‐surface proteins and suppression of the malignant phenotype. Design of organic antibody “mimetics” based on the structure of antireceptor antibodies may provide useful therapies and biological reagents to affect growth factor receptor function.