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Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer

C Knabbe, M E Lippman, L M Wakefield

    Cell
    |February 13, 1987
    PubMed

    Insights

    Transforming growth factor-beta (TGF-beta) is secreted by MCF-7 breast cancer cells and acts as a growth inhibitor. Antiestrogen treatment increases TGF-beta secretion, which can be blocked by antibodies.

    Area of Science:

    • Endocrinology
    • Molecular Biology
    • Cancer Research

    Background:

    • Hormone-dependent breast cancer cells, such as MCF-7, can secrete growth factors.
    • Transforming growth factor-beta (TGF-beta) plays a complex role in cancer biology.

    Purpose of the Study:

    • To investigate the secretion and role of TGF-beta in MCF-7 breast cancer cells.
    • To determine if antiestrogens influence TGF-beta secretion and activity.

    Main Methods:

    • MCF-7 cells were treated with antiestrogens.
    • TGF-beta levels in culture medium were measured.
    • Biological activity of secreted TGF-beta was assessed using growth assays and receptor binding.
    • Coculture experiments with an estrogen receptor-negative cell line were performed.
    • Neutralizing antibodies against TGF-beta were used.

    Main Results:

    • MCF-7 cells secrete biologically active TGF-beta that competes for receptor binding.
    • Antiestrogen treatment induced 8- to 27-fold increase in active TGF-beta secretion.
    • Antiestrogen-induced TGF-beta inhibited the growth of a different breast cancer cell line.
    • This growth inhibition was reversed by anti-TGF-beta antibodies.

    Conclusions:

    • TGF-beta is a hormonally regulated growth inhibitor in MCF-7 cells.
    • TGF-beta may function in autocrine and paracrine signaling pathways in breast cancer.

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