RRR-ALPHA-TOCOPHERYL SUCCINATE ENHANCES TGF-BETA(1), TGF-BETA(2), ANDTGF-BETA(3) AND TGF-BETA-R-II EXPRESSION BY HUMAN MDA-MB-435 BREAST-CANCER CELLS

The proliferation of MDA-MB-435 human breast cancer cells was inhibite d by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Condit ioned media (CM) from VES growth-inhibited cells contained potent anti proliferative activity, part of which is contributed by transforming g rowth factor-beta: (TGF-beta) isoforms. Antibody neutralization analys es, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta(1), -beta(2), and -beta(3) were present in the CM from VES-t reated cells. Culturing MDA-MB-435 cells with VES did not alter the le vels of constitutively expressed 2.4-kb TGF-beta(1), 3.0- and 4.0-kb T GF-beta(2), or 1.2- and 3.5-kb TGF-beta(3) mRNA transcripts. Inhibitio n of DNA synthesis by MDA-MB-435 cells was increased by combinations o f suboptimal levels of VES and purified TGF-beta(1). VES-treated MDA-M B-435 cells exhibited enhanced binding of radiolabeled TGF-beta(1), an d Western immunoblotting analyses showed that VES treatment enhanced T GF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated af ter four hours of treatment with VES, this treatment did not modify th e 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs . Results demonstrate that biologically active TGF-beta(1), -beta(2), -beta(3) and levels of TGF-beta type II receptor expressed by human br east cancer cells are enhanced by VES treatments.