ANTIESTROGENS INHIBIT THE REPLICATION OF THE RETROVIRAL MOLONEY MURINE LEUKEMIA-VIRUS IN-VITRO

Widely used in breast cancer therapy, tamoxifen exhibits in vitro and in vivo pleiotropic activities that are generally attributed to its bi nding to the estrogen receptor. However, several reports have shown th at the antiestrogen binding site (ABS) is also an intracellular target of the drug. This dual affinity determines at least two modes of acti on for the triphenylethylenic antiestrogens; one would be estrogen rev ersible and the other irreversible. Here, tamoxifen is shown to inhibi t the production of Moloney murine leukemia virus virions by fibroblas tic A9 cells, in which estrogen receptor is not detectable either by b inding or by radioimmunoassay. Moreover, a specific ligand of the ABS induces effects equivalent to those of tamoxifen, suggesting that tamo xifen inhibits Moloney murine leukemia virus replication through an es trogen-independent pathway involving the ABS.