Inhibition of tenascin-C expression in mammary epithelial cells by thyroidhormone

Multiple data suggest a relationship between thyroid hormone (triiodothyron ine (T3)) and carcinogenesis. Studies on breast cancer have been inconclusi ve, suggesting contradictory effects of thyroid status and diseases. Recent ly, we reported that expression of the extracellular matrix glycoprotein te nascin-C is modulated by T3 during rat brain development. Because tenascin- C has been reported to have growth-, motility-, and angiogenic-promoting ac tivities and to become upregulated during tumorigenesis in breast carcinoma and stromal cells, we analyzed the effects of T3 on tenascin-C expression in mammary epithelial cells. In this study, we showed that tenascin-C RNA e xpression was inhibited by T3 in normal un-transformed EpH4 mouse mammary e pithelial cells expressing appropriate receptors. T3's action appeared to b e due to a decreased half-life of the tenascin-C mRNA, with a maximum effec t (85% at 100 nM) 48 h after addition. T3 also downregulated tenascin-C in the human mammary tumor cell line SKBR-3, which expresses endogenous thyroi d receptors. Immunoprecipitation experiments confirmed that tenascin-C prot ein content was also decreased by T3 in EpH4 cells (70% reduction at 100 nM ). Dexamethasone had a similar inhibitory effect (70% at 100 nM), whereas e stradiol, the antiestrogen ICI 164,384, progesterone, and all-trans retinoi c acid did not alter tenascin-C expression. Our data demonstrate an inhibit ory action of T3 on tenascin-C expression in mammary epithelial cells that may play a role in the physiological regulation of this gene and in neoplas tic processes. Mot Carcinog. 24:99-107, 1999. (C) 1999 Wiley-Liss, Inc.