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Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar

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Summary

The hormone dependency of the MCF-7 breast cancer cell line, while extensively tested in liquid culture, has not been previously evaluated under conditions of anchorage-independent growth in serum-free media. Using the soft agar clonogenic assay, we demonstrate that physiologically relevant concentrations of estradiol (E2), progesterone (Pg), and prolactin (PRL) similarly stimulated MCF-7 cell colony formation in the absence of serum. Addition of an anti-insulin-like growth factor-I (IGF-I) antibody inhibited E2- and Pg-stimulated growth, while PRL action was not affected. Similar results were obtained with an anti-IGF-I receptor antibody, except that its inhibitory effect on Pg-induced colony formation was modest and not statistically significant. Administration of either an anti-transforming growth factor-α (TGF-α) antibody or an anti-epidermal growth factor (EGF) receptor antibody similarly inhibited E2-stimulated MCF-7 cell growth in soft agar, while neither antibody influenced Pg or PRL effects. Addition of TGF-β1, -β2, -β3 similarly suppressed MCF-7 cell colony formation in a dose dependent manner to a degree comparable to that observed with 4-OH-tamoxifen (4-OH-T). Furthermore, the growth inhibitory effect of 4-OH-T was completely reversed by an anti-TGF-β antibody. We conclude that IGFs and TGF-α are important mediators of E2-stimulated MCF-7 cell growth in soft agar. IGFs may also be playing a role in Pg action, while neither growth factor is involved in PRL-stimulated colony formation. Finally, TGF-β appears to be an important mediator of antiestrogen-induced inhibition of tumor growth.

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Abbreviations

IGF:

insulin-like growth factor

TGF:

transforming growth factor

E2 :

estradiol-17β

Pg:

progesterone

PRL:

prolactin

4-OH-T:

4-hydroxy-tamoxifen

IMEM:

improved minimal essential medium

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Authors and Affiliations

  1. Department of Medicine, The Pennsylvania State University, 17033, Hershey, PA, USA

    A. Manni & C. Wright

  2. Center for Biostatistics and Epidemiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, 17033, Hershey, PA, USA

    H. Buck

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  3. H. Buck
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Manni, A., Wright, C. & Buck, H. Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar. Breast Cancer Res Tr 20, 43–52 (1991). https://doi.org/10.1007/BF01833356

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