Regulation of transforming growth factor alpha and transforming growth factor beta messenger ribonucleic acid abundance in T-47D, human breast cancer cells.
Both transforming growth factor beta (TGF beta) and TGF alpha mRNA are expressed in human breast cancer cell lines. We have investigated the relationship of mRNA abundance for these growth modulators to the proliferation rate of a number of human breast cancer cell lines. Furthermore, we have investigated the relationship of regulation of TGF beta and TGF alpha mRNA to growth inhibition caused by progestins and nonsteroidal antiestrogens in T-47D human breast cancer cells. The abundance of TGF beta and TGF alpha mRNA in human breast cancer cell lines was not related directly to proliferation rate of the cells in culture or estrogen receptor positivity or negativity. The relationship of TGF beta and TGF alpha mRNA to growth inhibition caused by antiestrogens and progestins was investigated in T-47D human breast cancer cells. We observed that in T-47D human breast cancer cells the abundance of TGF beta mRNA is decreased in a time- and dose-dependent fashion by progestins but remains unaltered by nonsteroidal antiestrogens. Treatment of T-47D cells for 24 h with 10 nM medroxyprogesterone acetate (MPA) reduced the level of TGF beta mRNA to one third that present in untreated cells. The same treatment increased TGF alpha mRNA 3-fold above untreated controls in a time- and dose-dependent fashion and nonsteroidal antiestrogens caused a small decrease. The regulation of both TGF alpha and TGF beta mRNA was not directly related to inhibition of growth by progestins and antiestrogens in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Murphy
L C
LC
Department of Biochemistry, University of Manitoba, Winnipeg, Canada.
Dotzlaw
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D012333:RNA, Messenger / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics; D015291:Transforming Growth Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000032:analysis
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D011987:Receptors, Steroid; D015291:Transforming Growth Factors; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone