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- W2316500543 abstract "Summary Transforming growth factor-βs (TGF-βs) are potent regulators of cell growth and differentiation. Expression of the closely related TGF-β subtypes in vivo is differentially regulated both temporally and spatially. Members of the steroid hormone superfamily may play an important role in this gene- and tissue-specific regulation. We have shown that anti-estrogens induce the production of TGF-β1 in mammary carcinoma cells and fetal fibroblasts, whereas retinoic acid specifically induces TGF-β2 in primary epidermal keratinocytes. The induction of TGF-β2 by retinoids is accompanied by an increase in TGF-β2 mRNAs, but little change in transcription rates, suggesting an effect of retinoids on message stability or processing. In contrast, TGF-β1 mRNA levels are unchanged by anti-estrogen treatment, suggesting these compounds may regulate the translatability of the TGF-β1 message or some post-translational processing event. We have identified a stable stem–loop structure in the 5′ untranslated region (UTR) of the TGF-β1 mRNA that inhibits translation of a heterologous reporter gene, and we are investigating the possibility that anti-estrogens may regulate the activity of this element, and hence the translatability of the TGF-β1 message. A significant fraction (25–90 %) of the TGF-β induced by retinoids and anti-estrogens is in the biologically active rather than the latent form. We have shown that active TGF-β has a much shorter in vivo half-life than latent TGF-β, suggesting that the TGF-β induced by retinoids and steroids may act locally at the site of production. Since many tumor cells retain sensitivity to the growth inhibitory effects of active TGF-β, the use of members of the steroid hormone superfamily for inducing this potent growth inhibitor locally at the tumor site may have therapeutic potential." @default.
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- W2316500543 date "1990-01-01" @default.
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- W2316500543 title "Regulation of transforming growth factor-<i>β</i> subtypes by members of the steroid hormone superfamily" @default.
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- W2316500543 doi "https://doi.org/10.1242/jcs.1990.supplement_13.13" @default.
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