Filla M S, Kaul K L
Department of Pathology, Northwestern University, Evanston Hospital, IL 60201, USA.
Placenta. 1997 Jan;18(1):17-27. doi: 10.1016/s0143-4004(97)90067-9.
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.
研究了转化生长因子-α（TGF-α）-表皮生长因子受体（EGFR）相互作用在调节良性和恶性滋养层细胞增殖中的作用。良性细胞滋养层（CT）对TGF-α有促有丝分裂刺激反应；BeWo和JAr绒毛膜癌细胞系无反应。通过酶联免疫吸附测定（ELISA）确定BeWo和JAr中的EGFR水平比良性CT中的至少高10倍。从BeWo和JAr分离的EGFR也显示出功能性酪氨酸激酶活性。使用免疫过氧化物酶（IP）和ELISA技术相结合的方法，发现绒毛膜癌细胞产生大量TGF-α，其与本实验室先前报道的良性CT中的TGF-α量相当，并认为是以自分泌方式刺激其自身增殖。EGFR阻断抗体和TGF-α中和抗体抑制JAr细胞增殖，而EGF中和抗体则无此作用。本文及我们先前报告中的数据表明，TGF-α-EGFR自分泌环可能调节正常和恶性CT的增殖。绒毛膜癌细胞可能部分由于EGFR过表达而以最大速率增殖，因此无法对外源生长因子产生进一步反应。因此，EGFR过表达可能总体上导致绒毛膜癌细胞的失控增殖。
