Antiestrogens inhibit the replication of the retroviral Moloney murine leukemia virus in vitro

C Chailleux, F Mesange, F Bayard, AC Prats and JC Faye

Institut Louis Bugnard, Contrat Jeune Formation INSERM 9103, Laboratoire d'Endocrinologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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

Volume 44, Issue 2, pp. 324-327, 08/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics