TAMOXIFEN INDUCES TGF-BETA-1 ACTIVITY AND APOPTOSIS OF HUMAN MCF-7 BREAST-CANCER CELLS IN-VITRO

We report here that the antiestrogen tamoxifen (TAM) induces cell deat h in human breast cancer cell line MCF-7. We assessed the type of cell death induced by TAM in this breast cancer cell line on the basis of morphological and biochemical characteristics. Dying cells showed morp hological characteristics of apoptosis, such as chromatin condensation and nuclear disintegration. DNA isolated from these cells revealed a pattern of distinctive DNA bands on agarose gel. The DNA fragmentation in MCF-7 cells induced by TAM could also be detected by terminal deox ynucleotidyl transferase-mediated dUTP-biotin end labeling. Northern b lot hybridization revealed a substantial increase in the amounts of TR PM-2 and TGF-beta 1 mRNAs in MCF-7 cells after treatment with TAM. In contrast, the mRNA level of the estrogen-induced pS2 gene was strongly suppressed. The biological activity of TGF-beta was increased at leas t fourfold in the media from MCF-7 cells treated with TAM. The results presented in this study suggest that TAM induces apoptosis of MCF-7 c ells and it may be mediated by the secretion of active TGF-beta. (C) 1 996 Wiley-Liss, Inc.