Antiproliferative effect of phorbol esters on MCF-7 human breast adenocarcinoma cells: relationship with enhanced expression of transforming growth-factor-beta 1.
In human breast carcinoma MCF-7 cells, phorbol diesters inhibit proliferation and induce cell maturation. We have recently reported that exogenous TGF-beta 1 reverses the resistance of a breast adenocarcinoma MCF-7 subline (MCF-7:RPh-4) to these phorbol ester effects. Here, we investigated the involvement of TGF-beta 1 in the PKC-mediated inhibition of breast-cancer cell proliferation. Parental MCF-7-conditioned medium contained a 20-fold higher transforming activity on NRK-49F fibroblasts than the TPA-resistant subline. TPA increased TGF-beta activity in MCF-7 conditioned medium. MCF-7 cells also expressed more TGF-beta 1 mRNA than the resistant subline. TPA induced a dose-dependent increase in TGF-beta 1 mRNA levels that paralleled the inhibitory effect on MCF-7 proliferation. The lower level of TGF-beta mRNA expression in TPA resistant subline was not modified after addition of TPA, but was significantly increased in the presence of exogenous TGF-beta 1. These data argue in favor of a role of endogenous TGF-beta 1 in the maturation process induced by protein kinase C activation.
Guerrin
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Laboratoire de Pharmacologie et Toxicologie Fondamentales, C.N.R.S., Toulouse, France.
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D000230:Adenocarcinoma; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D010957:Plasmids; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate