Prostaglandin synthesis and binding is increased in regressing NMU mammary carcinoma.

Abstract Mammary tumors induced in Buffalo rats by treatment with nitrosomethyl urea will regress after oophorectomy. Their ability to synthesize and bind prostaglandins E and F 2 α was studied in the growing and regressing states. Prostaglandins present in suspensions of 100,000 xg tumor membranes after 2 hr incubation at 37°C ± 5×10 −4 M indomethacin were partially purified by silica gel column chromatography before assay by specific PG RIA. The amounts of PGE and F 2 α synthesized rose from 0.13 and 10.5 ng/mg protein in the growing tumors to a maximum of 1.2 and 26.5 ng/mg protein 5 days after oophorectomy. Specific binding of 3 H-PGE 2 and 3 H-PGF 2 α to 15,000 xg tumor membranes was achieved during a 45 min incubation at 23°C ± excess unlabelled PG. Free and bound prostaglandins were separated by filtration. Binding reached equilibrium after 30 min, was saturable and reversible. Scatchard analysis revealed high affinity binding of PGF 2 α but only low affinity PGE 2 binding in membranes obtained from growing tumors. A 2–3-fold increase in specific binding of PGE 2 and PGF 2 α was noted at 4 days after oophorectomy which represented an increase in the number of PGF 2 α receptors. PGE 2 binding retained a low affinity character. The elevated PGF 2 α synthesis rates observed in the regressing tumors coupled with a regression-associated increase in receptor number suggests that PGF 2 α-plays a significant role in hormone-dependent mammary tumor regression.