Prolactin receptors in explant cultures of carcinogen-induced rat mammary tumors.

The turnover, down-regulation and role of intracellular organelles in the down-regulation of prolactin (PRL) receptors have been investigated in N-nitrosomethylurea (NMU)-induced rat mammary tumors cultured in short-term explants. Tumor explants are capable of maintaining PRL receptors for 24-48 hr. This maintenance reflects a dynamic phenomenon involving receptor synthesis, since addition of cycloheximide (1 microgram/ml) in the culture medium results within 12 hr in a marked decline of PRL receptor levels. A down-regulation of total PRL receptors (measured after exposure of membranes to 3M MgCl2) is observed in cultures containing concentrations of 20 micrograms/ml or greater of ovine PRL (oPRL). Lysosomotropic agents, such as chloroquine (100 microM) are ineffective in either increasing basal PRL receptor levels or in preventing the PRL-induced down-regulation in NMU-induced mammary tumor explants. Cytochalasin B (20 microM), without effect on basal PRL binding, prevents the down-regulation of PRL receptors, whereas colchicine (10 microM) results in a decline of PRL receptor levels both in the absence and in the presence of oPRL. The present data suggest a different pattern of PRL receptor regulation in vitro for tumors compared to normal rabbit mammary explants.