Regulation of transforming growth factor α and transforming growth factor β messenger ribonucleic acid abundance in T-47D, human breast cancer cells

Abstract

Both transforming growth factor β (TGFβ) and TGFα 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 TGFβ and TGFα mRNA to growth inhibition caused by progestins and nonsteroidal antiestrogens in T-47D human breast cancer cells. The abundance of TGFβ and TGFα 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 TGFβ and TGFα 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 TGFβ 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 TGFβ mRNA to one third that present in untreated cells. The same treatment increased TGFα mRNA 3-fold above untreated controls in a time- and dose-dependent fashion and nonsteroidal antiestrogens caused a small decrease. The regulation of both TGFα and TGFβ mRNA was not directly related to inhibition of growth by progestins and antiestrogens in T-47D cells. Furthermore, the significance of the expression of TGFβ to any autocrine effect on these cells is unclear since we were unable to detect any high affinity TGFβ receptors on the cell surface of T-47D cells. Our data are not consistent with the hypothesis that TGFβ and TGFa function directly as autocrine modulators in T-47D cells when these cells are grown under conditions which result in progestin-induced growth inhibition. © 1989 by The Endocrine Society.