Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar |
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Authors: | A. Manni C. Wright H. Buck |
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Affiliation: | (1) Department of Medicine, The Pennsylvania State University, 17033 Hershey, PA, USA;(2) Center for Biostatistics and Epidemiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, 17033 Hershey, PA, USA |
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Abstract: | 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- (TGF-) 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-1, -2, -3 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- antibody. We conclude that IGFs and TGF- 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- appears to be an important mediator of antiestrogen-induced inhibition of tumor growth.Abbreviations IGF insulin-like growth factor - TGF transforming growth factor - E2 estradiol-17 - Pg progesterone - PRL prolactin - 4-OH-T 4-hydroxy-tamoxifen - IMEM improved minimal essential medium |
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Keywords: | insulin-like growth factors hormonally regulated growth MCF-7 breast cancer cell line transforming growth factors /content/t92643j573142k73/xxlarge945.gif" alt=" agr" align=" BASELINE" BORDER=" 0" > and /content/t92643j573142k73/xxlarge946.gif" alt=" beta" align=" MIDDLE" BORDER=" 0" > estrogen progesterone prolactin |
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