Regulation of the levels of three transforming growth factor beta mRNAs by estrogen and their effects on the proliferation of human breast cancer cells.
Transforming growth factor (TGF) beta is a potent regulator of cell proliferation and may play a role in breast cancer cell growth. We have evaluated the regulation of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs by 17 beta-estradiol (E2) and 4-hydroxytamoxifen (MOH) in estrogen receptor-positive (ER(+)) MCF-7 and estrogen receptor-negative (ER(-)) MDA-MB-231 human breast cancer cells. We also determined the effect of TGF beta 1, TGF beta 2, and TGF beta 3 on the proliferation of these cells. Cells were deprived of estrogen before the addition of hormones, and mRNA was measured by Northern blot analysis. We found that MCF-7 cells expressed mRNAs of all three TGF beta species. Treatment of MCF-7 cells with 10(-10) M E2 for 7 days resulted in a dramatic decrease in the TGF beta 2 and TGF beta 3 mRNA levels, but not in the TGF beta 1 mRNA level. MOH was found to block these effects. In addition, the regulation of TGF beta 2 and beta 3 gene expression occurs at both transcriptional and post-transcriptional levels. There is an inverse correlation between E2-induced growth and levels of TGF beta 2 and TGF beta 3 mRNA. In contrast to MCF-7 cells, MDA-MB-231 cells expressed TGF beta 1 and TGF beta 2 mRNAs but TGF beta 3 mRNA was not detected, and the TGF beta 1 and TGF beta 2 mRNAs were not regulated by estrogens or antiestrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
Jeng
M H
MH
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison 53792.
ten Dijke
P
P
Iwata
K K
KK
Jordan
V C
VC
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D004967:Estrogens; D011980:Receptors, Progesterone; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol