Interactions between growth factor secretion and polyamines in MCF-7 breast cancer cells.
Polyamines may be involved in hormone-dependent breast cancer cell proliferation. The antiestrogen 4-hydroxy-tamoxifen and the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO) inhibited MCF-7 growth, and this effect was additive. Transforming growth factor beta (TGF-beta) levels were increased by both compounds; again the effect was additive. Exogenous putrescine antagonized DFMO but not the antiestrogen. However, exogenous TGF-beta did not inhibit cell growth. Secretion of insulin-like growth factor 1 (IGF-1) was not affected by DFMO-induced polyamine depletion but 4-hydroxytamoxifen increased IGF-1, which suggests an estradiol-like effect. Thus polyamines are involved in basal TGF-beta secretion but do not mediate antiestrogen-induced TGF-beta secretion. IGF-1 secretion by MCF-7 cells is not under polyamine control. The antiproliferative effects of 4-hydroxytamoxifen and DFMO cannot be accounted for by either suppression of IGF-1 secretion (a growth stimulatory factor) or stimulation of TGF-beta production (a growth inhibitory polypeptide).
Cohen
F J
FJ
Division of Endocrinology, Milton S. Hershey Medical Center, Hershey, PA 17033.
Manni
A
A
Glikman
P
P
Bartholomew
M
M
Demers
L
L
D001943:Breast Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D011073:Polyamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004965:Estrogen Antagonists; D011073:Polyamines; D013002:Somatomedins; D013629:Tamoxifen; C016601:afimoxifene; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D000518:Eflornithine