INHIBITORY-ACTION OF REVEROMYCIN-A ON TGF-ALPHA-DEPENDENT GROWTH OF OVARIAN-CARCINOMA-BG-1 IN-VITRO AND IN-VIVO

The antitumor effect of reveromycin A (RM-A), an inhibitor of EGF-depe ndent cell proliferation on murine and human tumor cell lines, was exa mined in vitro and in vivo. In vivo, RM-A showed little antitumor effe ct against three murine tumors tested, but showed strong antitumor eff ect (a minimum treated/control ratio of 36%) against a human ovarian c arcinoma BG-1, which is known to be a transforming growth factor alpha (TGF-alpha)-secreting and estrogen receptor-expressing cell line. In BG-1 cells, RM-A inhibited the cell proliferation induced by TGF-alpha at the concentration range 30-300 nM, but did not inhibit the prolife ration induced by 17 beta-estradiol (E-2). RM-A is a possible new anti tumor drug with a novel mechanism of action and may also be a useful t ool for the analysis of epidermal growth factor receptor (EGFR)-mediat ed cell proliferation in tumor cells.