Relative expression of epidermal growth factor receptor in placental cytotrophoblasts and choriocarcinoma cell lines

The role of transforming growth factor-alpha (TGF-alpha)-epidermal growth factor receptor (EGFR) interactions in regulating benign and malignant trophoblast proliferation were examined. Benign cytotrophoblast (CT) demonstrated mitogenic stimulation in response to TGF-alpha; BeWo and JAr choriocarcinoma cell lines failed to respond. EGFR levels in BeWo and JAr were determined by enzyme linked immunoassay (ELISA) to be at least 10-fold higher than those in benign CT. EGFR isolated from BeWo and JAr also demonstrated functional tyrosine kinase activity. Using a combination of immunoperoxidase (IP) and ELISA techniques, choriocarcinoma cells were found to produce significant quantities of TGF-alpha that were comparable with those reported previously by this laboratory for benign CT, and were felt to be stimulating their own proliferation in an autocrine fashion. EGFR blocking and TGF-alpha neutralizing antibodies inhibited JAr proliferation whereas an EGF neutralizing antibody did not. The data presented here and in our previous report indicate that a TGF-alpha-EGFR autocrine loop may regulate normal and malignant CT proliferation. Choriocarcinoma cells may be proliferating at a maximal rate due, in part, to EGFR overexpression and are therefore unable to respond further to exogenous growth factor. Thus, EGFR overexpression may contribute to the uncontrolled proliferation of choriocarcinoma cells in general.