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 Agar

Andrea Manni, Carol Wright, Betty Badger, Laurence Deniers, James Lynch

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11 Scopus citations

Abstract

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 (α 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 α 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 a 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.

Original languageEnglish (US)
Pages (from-to)7179-7183
Number of pages5
JournalCancer Research
Volume50
Issue number22
StatePublished - Nov 12 1990

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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