Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily

L. Wakefield, S. J. Kim, Adam Bleier Glick, T. Winokur, A. Colletta, M. Sporn

Research output: Contribution to journalArticle

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Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalJournal of Cell Science
Volume97
Issue numberSUPPL. 13
StatePublished - Dec 1 1990

Fingerprint

Retinoids
Transforming Growth Factors
Estrogens
Steroids
Hormones
Growth Inhibitors
Messenger RNA
5' Untranslated Regions
Protein Biosynthesis
Growth
Tretinoin
Keratinocytes
Reporter Genes
Half-Life
Cell Differentiation
Neoplasms
Fibroblasts
Breast Neoplasms
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Wakefield, L., Kim, S. J., Glick, A. B., Winokur, T., Colletta, A., & Sporn, M. (1990). Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily. Journal of Cell Science, 97(SUPPL. 13), 139-148.
Wakefield, L. ; Kim, S. J. ; Glick, Adam Bleier ; Winokur, T. ; Colletta, A. ; Sporn, M. / Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily. In: Journal of Cell Science. 1990 ; Vol. 97, No. SUPPL. 13. pp. 139-148.
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Wakefield, L, Kim, SJ, Glick, AB, Winokur, T, Colletta, A & Sporn, M 1990, 'Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily', Journal of Cell Science, vol. 97, no. SUPPL. 13, pp. 139-148.

Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily. / Wakefield, L.; Kim, S. J.; Glick, Adam Bleier; Winokur, T.; Colletta, A.; Sporn, M.

In: Journal of Cell Science, Vol. 97, No. SUPPL. 13, 01.12.1990, p. 139-148.

Research output: Contribution to journalArticle

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Wakefield L, Kim SJ, Glick AB, Winokur T, Colletta A, Sporn M. Regulation of transforming growth factor-β subtypes by members of the steroid hormone superfamily. Journal of Cell Science. 1990 Dec 1;97(SUPPL. 13):139-148.