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).