COEXPRESSION OF EPIDERMAL GROWTH FACTOR-RECEPTOR AND C-ERBB-2 PROTOONCOGENE PRODUCT IN HUMAN SALIVARY-GLAND ADENOCARCINOMA CELL-LINE HSG AND THE IMPLICATIONS FOR HSG CELL AUTOCRINE GROWTH

The autonomous proliferation of HSG cells is mediated by an autocrine growth factor, a 46K epidermal growth factor (EGF)-like molecule. The receptor for this molecule was investigated. Immunoprecipitation and immunoblotting revealed the expression of two possible receptor molecules, EGF-R and p185(erbB-2), in HSG cells. Northern blotting also revealed the co-expression of 5.6-kb EGF-R mRNA and 4.6-kb c-erb B-2 mRNA. When the purified EGF-like molecule was added to the cultures, EGF-R but not pl85(erbB-2) was autophosphorylated. These results suggest that, although both EGF-R and p185(erbB-2) are co-expressed in HSG cells, the EGF-R is the genuine receptor for the EGF-like molecule. However, there is a possibility that p185(erbB-2) is involved in the signal transduction system. This possibility was examined by using specific antibodies to human EGF-R (hEGF-R), p185(erbB-2), and EGF to inhibit the functions of these molecules. Addition of these three antibodies to the cultures inhibited the growth of HSG cells. The antibodies to EGF-R and p185(erbB-2) also caused morphological changes such as disturbances of the plasma membrane, and some cell death. Surprisingly, the effect of the anti-p185(erbB-2) antibody on growth inhibition and morphology was stronger than that of the anti-hEGF-R antibody. Thus, p185(erbB-2) expressed in HSG cells has an important function in the signal transduction of HSG cell growth.