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 death 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 morphological 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 deoxynucleotidyl transferase-mediated dUTP-biotin end labeling. Northern blot hybridization revealed a substantial increase in the amounts of TRPM-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 least 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 cells and it may be mediated by the secretion of active TGF-beta.
Chen
H
H
Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405, USA.
Tritton
T R
TR
Kenny
N
N
Absher
M
M
Chiu
J F
JF
D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D002847:Chromatography, Agarose; D051152:Clusterin; D004273:DNA, Neoplasm / Q000187:drug effects; D004967:Estrogens / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C495242:CLU protein, human; D051152:Clusterin; D004273:DNA, Neoplasm; D004967:Estrogens; D006023:Glycoproteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011506:Proteins; C051838:TFF1 protein, human; D016212:Transforming Growth Factor beta; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen