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Role of Insulin-like Growth Factor-related Peptides in the Estradiol-, Prolactin-, and Progesterone-stimulated Growth of N-Nitrosomethylurea-induced Rat Mammary Tumors in Soft Agar¹

Departments of Medicine [A. M., C. W., B. B.] and Pathology [L. D.] and Center for Biostatistics and Epidemiology [J. L.], The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033

The present experiments were designed to test the role of insulin-like growth factor-related peptides (IGF-RPs) in hormonally stimulated N-nitrosomethylurea (NMU)-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 ( 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 (E₂)-, prolactin (PRL)-, and progesterone (Pg)-treated NMU-induced rat mammary tumors. Both Abs abolished the colony-stimulating action of genuine insulin-like growth factor I while having no effect when added alone or with control CM. The addition of either 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 NMU mammary tumor cells exposed to these hormones. Next, we directly tested the role of IGF-RPs as mediators of hormonally stimulated growth. We indeed observed that the addition of sm 1.20B markedly inhibited the colony-stimulating actions of E₂, 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 produced upon exposure to E₂, PRL, and Pg, but also are important mediators of hormonally stimulated growth.

¹ This work is supported by a grant from the National Cancer Institute, P01 CA40011.

² To whom requests for reprints should be addressed, at Division of Endocrinology, The Milton S. Hershey Medical Center, P. O. Box 850, Hershey, PA 17033.

Received 2/12/90. Accepted 8/16/90.