Role of Insulin-like Growth Factor-related Peptides in the Estradici-, Prolactin-, and Progesterone-stimulated Growth of yV-Nitrosomethylurea-induced Rat Mammary Tumors in Soft Agar 1

The present experiments were designed to test the role of insulin-like growth factor-related peptides (It.I KIM in hormonal!} stimulated V nitrosomethylurea (NML')-induced mammary tumor colony formation in soft agar. To evaluate production of IGF-RP by NMU cells, we tested the abilities of a monoclonal antibody directed against insulin-like growth factor I (a sm 1.20B) and of a polyclonal antibody raised against the insulin-like growth factor I (Ab 134) to inhibit the colony-stimulating effects of conditioned media (CM) obtained from estradiol (E;)-, prolactin (PRL)-, and progesterone (Pg)-treated »Mil-induced rat mammary tu mors. Both Abs abolished the colony-stimulating action of genuine insu lin-like growth factor I while having no effect when added alone or with control CM. The addition of either a sm 1.20B or Ab 134 (but not that of an irrelevant Ab) consistently blocked the colony-stimulating action of E2-CM, PRL-CM, and Pg-CM, suggesting that IGF-RPs are produced by NMLÕmammary tumor cells exposed to these hormones. Next, we directly tested the role of IGF-RPs as mediators of hormonally stimulated growth. \Vc indeed observed that the addition of a sm I.20B markedly inhibited the colony-stimulating actions of 1 . PRL, and Pg added to NMU mammary tumor cells in soft agar in the absence of serum. We conclude that, in our experimental system, IGF-RPs not only are pro duced upon exposure to I-'..,PRL, and Pg, but also are important media tors of hormonally stimulated growth.

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