Positive and Negative Modification of Dexamethasone-Mediated MMTV gp52 Release by Progesterone Pretreatment of Tumor Cells

Abstract

Murine mammary tumor cells (C3H Mm5mt/cl) were grown in charcoal-stripped serum to examine the effects of hormonal treatments on the expression and release of the mouse mammary tumor virus (MMTV) envelope glycoprotein (gp52). The ability of progesterone to modify extracellular levels of soluble and virion-associated MMTV gp52 was tested singly and as a pretreatment prior to dexamethasone (DXS) stimulation. Single treatments with DXS or progesterone demonstrated that DXS was substantially more effective at elevating gp52 than progesterone; however, a small but significant increase in gp52 levels was noted after 72 h of progesterone treatment. Progesterone pretreatments at 10- to 100-fold excess of DXS altered subsequent DXS-stimulated gp52 levels. Progesterone effectively antagonized DXS and reduced gρ52 levels to those of controls but this reduction was accomplished only at the lowest concentrations of DXS (10^–8M) and shortest treatment interval (24 h). While some pretreatment protocols of varied dose slightly reduced gp52 levels at a point in time after treatment, the majority of progesterone pretreatments at 10^–7,10^–6, and 10^–5M resulted in MMTV gp52 levels which were equal to and in many cases significantly greater than those obtained with DXS alone. The ability to augment DXS-stimulated gp52 levels with progesterone pretreatment suggests that, under certain hormonal conditions, gp52 expression and release from mouse cells may be progesterone-dependent as well as glucocor-ticoid-dependent.