TAMOXIFEN ANTAGONIZES PROLIFERATION AND INVASION OF ESTROGEN RECEPTOR-NEGATIVE METASTATIC FOLLICULAR THYROID-CANCER CELLS VIA PROTEIN-KINASE-C

Tamoxifen inhibits invasion and growth of estrogen-receptor negative f ollicular thyroid cancer (FTC) cells in vitro and in vivo. To study th e mechanisms involved, we documented tile effects of tamoxifen and sta urosporine on three metastatic FTC-cell lines. TPA(10 ng/ml) enhanced invasion and growth of FTC by 15% (P < 0.02). Tamoxifen (1.5 mu mol/l) inhibited invasion of FTC133 by 36% (FTC236 30%; FTC238 32%; P < 0.01 ). TPA reversed the tamoxifen-mediated inhibition of invasion by 35% i n FTC133 and 30% in FTC238 (P < 0.02). Staurosporine (10 ng/ml) inhibi ted invasion and growth of all FTC. At 0.1-1 ng/ml it enhanced the inh ibitory effects of tamoxifen, but did not further inhibit invasion or growth at higher concentrations. We conclude that the antiproliferativ e and antiinvasive effects of tamoxifen on follicular thyroid cancer c ells are at least partly mediated by an inhibition of protein kinase C .