title: Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar.
abstract: 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-alpha (TGF-alpha) 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-beta 1, -beta 2, -beta 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-beta antibody. We conclude that IGFs and TGF-alpha 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-beta appears to be an important mediator of antiestrogen-induced inhibition of tumor growth.
authors.affiliation: Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
authors.forename: A
authors.initials: A
authors.lastname: Manni
authors.forename: C
authors.initials: C
authors.lastname: Wright
authors.forename: H
authors.initials: H
authors.lastname: Buck
mesh_terms: D000362:Agar; D000906:Antibodies; D001943:Breast Neoplasms / Q000473:pathology*; D003470:Culture Media; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
chemical_list: D000906:Antibodies; D003470:Culture Media; D006133:Growth Substances; D006728:Hormones; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; C016601:afimoxifene; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D000362:Agar; D011388:Prolactin