Multihormonal regulation of insulinlike growth factor-i-related protein in mcf-7 human breast cancer cells

Karen K. Huff, Cornelius Knabbe, Ralph Lindsey, Dwight Kaufman, Diane Bronzed, Marc E. Lippman, Robed B. Dickson

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

MCF-7 human breast cancer cells have been studied for hormonal regulation of secretion of an insulin growth factor-I (IGF-I)-related growth factor. 17β-Estradiol, which is required for tumorigenesis of the cell line in the nude mouse and which stimulates proliferation in vitro, was able to significantly induce IGF-I secretion at 10-13 M, with maximal induction at 10-11 M. Under optimal conditions IGF-I could be induced 4-fold after 4 days. Demonstration of estrogenic stimulations required removal of phenol red, a weak estrogen, from the cell culture medium. In addition to estrogen, insulin, epidermal growth factor, and transforming growth factor α induce both cellular proliferation and IGF-I secretion, while growth inhibitory antiestrogens, transforming growth factor β, and glucocorticoids have the opposite effect. In each case, modulations in IGF-I secretion preceeded effects on cellular proliferation. IGF-I was not regulated by human GH, basic fibroblast growth factor, platelet-derived growth factor, or PRL, none of which affected proliferation rate. Thus, regulation of IGF-I secretion in human breast cancer is controlled by different hormones from those previously reported in human fibroblasts. Regulation of IGF-I by neither estrogen nor antiestrogen was associated with changes in steady-state mRNA levels; thus regulation may occur at a step beyond mRNA. We conclude that IGF-I production is tightly coupled to growth regulation by estrogens, antiestrogens, and other hormones and may contribute to autocrine and/or paracrine growth regulation by these agents in breast cancer.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalMolecular Endocrinology
Volume2
Issue number3
DOIs
StatePublished - Mar 1988

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Huff, K. K., Knabbe, C., Lindsey, R., Kaufman, D., Bronzed, D., Lippman, M. E., & Dickson, R. B. (1988). Multihormonal regulation of insulinlike growth factor-i-related protein in mcf-7 human breast cancer cells. Molecular Endocrinology, 2(3), 200-208. https://doi.org/10.1210/mend-2-3-200