N-nitroso-N-methylurea-induced mammary carcinogenesis: effect of prolactin on expression of Ia antigen by tumor cells.

Prolactin (PRL) increases of Ia antigen (Ia Ag) expression in female Sprague-Dawley rats with N-nitroso-N-methylurea [(NMU) CAS: 684-93-5]-induced mammary tumors were studied. The effectiveness of PRL was examined when cancers appeared about 2-3 months after the first NMU administration. Rats with NMU-induced mammary tumors were divided into 3 groups: Group 1 was treated with 30 micrograms ovine PRL (o-PRL) in daily sc injections for 5 days. Group 2 received 0.5 mg 2 alpha-bromoergocryptine (CB-154), a known inhibitor of pituitary gland secretion, daily in sc injections for 6 days. Group 3 was the control group. Ia Ags expressed by NMU-induced mammary tumor cells were then quantified successively by double labeling [protein membrane cells with iodine-131 and anti-Ia monoclonal antibody (MoAb) with iodine-125]; then isolation and quantification of the doubly labeled immune complex were performed by affinity chromatography and chromatofocusing successively. When the specific activity of glycoproteins is known, the amount of glycoproteins that bind specifically to the anti-Ia MoAb can be deduced. In NMU-induced rat mammary tumor controls, about 5% of the purified glycoproteins bound specifically to the MoAb, and the amount increased to 8% for NMU-induced rat mammary tumors treated with 30 micrograms o-PRL daily for 5 days and decreased to 2.5% in NMU-induced rat mammary tumors treated with 0.5 mg CB-154 daily for 6 days. Total PRL receptor levels were measured in all tumors tested. For control NMU-induced rat mammary tumors, total PRL receptor levels were 6.35 +/- 1.40 fmol/mg protein, 7.20 +/- 2.40 fmol/mg protein for NMU-induced rat mammary tumors treated with o-PRL, and 6.81 +/- 2.34 fmol/mg protein for NMU-induced rat mammary tumors treated with CB-154. Our results demonstrated that treatment of NMU-induced rat mammary tumors with PRL increased the amount of Ia Ag expression by tumor cells and should prove very useful to the understanding of the biology of PRL in the tumorogenesis of the mammary gland.