Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression - PubMed (original) (raw)

Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression

B Raught et al. Mol Endocrinol. 1995 Sep.

Abstract

A highly conserved CCAAT/enhancer-binding protein (C/EBP)-binding site centered around -134 relative to the transcription start site in the rat beta-casein gene promoter is capable of interacting specifically with recombinant and mammary gland C/EBP proteins. Western blot analysis indicates that C/EBP levels change dramatically throughout mammary gland development. C/EBP alpha expression is barely detectable in mammary glands from virgin and pregnant animals but is expressed at high levels during lactation and at lower levels during involution. The expression of three C/EBP beta isoforms [the liver-enriched activating proteins (LAPs); and the liver-enriched inhibiting protein (LIP)] is elevated throughout pregnancy, with LIP expression increasing more than 100-fold. Thus, during pregnancy, a low LAP/LIP ratio (< 5) is maintained. C/EBP beta expression decreases at parturition, with LIP diminishing to levels observed in the virgin gland. Therefore, during lactation a more than 100-fold increase in the LAP/LIP ratio is observed. Treatment of the HC11 mammary epithelial cell line with hydrocortisone results in a 10- to 20-fold inhibition of LIP expression, with only minor changes in LAP levels. Therefore, glucocorticoids may impinge upon beta-casein gene expression by altering the ratio of the inhibitory to the activating isoforms of C/EBP beta. Several previously defined casein gene promoter regions capable of conferring hormone and extracellular matrix inducibility to reporter genes in mammary cells are suggested to be composite response elements, containing putative binding sites for the same set of hormonally and developmentally regulated factors: C/EBP, MGF/Stat5, and the glucocorticoid receptor.

PubMed Disclaimer

Cited by

The Role of CYP3A in Health and Disease.
Klyushova LS, Perepechaeva ML, Grishanova AY. Klyushova LS, et al. Biomedicines. 2022 Oct 24;10(11):2686. doi: 10.3390/biomedicines10112686. Biomedicines. 2022. PMID: 36359206 Free PMC article. Review.
C/EBPβ isoform-specific regulation of migration and invasion in triple-negative breast cancer cells.
Sterken BA, Ackermann T, Müller C, Zuidhof HR, Kortman G, Hernandez-Segura A, Broekhuis M, Spierings D, Guryev V, Calkhoven CF. Sterken BA, et al. NPJ Breast Cancer. 2022 Jan 18;8(1):11. doi: 10.1038/s41523-021-00372-z. NPJ Breast Cancer. 2022. PMID: 35042889 Free PMC article.
C/EBPß Isoform Specific Gene Regulation: It's a Lot more Complicated than you Think!
Spike AJ, Rosen JM. Spike AJ, et al. J Mammary Gland Biol Neoplasia. 2020 Mar;25(1):1-12. doi: 10.1007/s10911-020-09444-5. Epub 2020 Feb 20. J Mammary Gland Biol Neoplasia. 2020. PMID: 32078094 Free PMC article. Review.
C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
Nacht AS, Ferrari R, Zaurin R, Scabia V, Carbonell-Caballero J, Le Dily F, Quilez J, Leopoldi A, Brisken C, Beato M, Vicent GP. Nacht AS, et al. EMBO J. 2019 Sep 16;38(18):e101426. doi: 10.15252/embj.2018101426. Epub 2019 Aug 2. EMBO J. 2019. PMID: 31373033 Free PMC article.
C/EBPβ Deletion Promotes Expansion of Poorly Functional Intestinal Regulatory T Cells.
Collins CB, Puthoor PR, Nguyen TT, Strassheim D, Jedlicka P, Friedman JE, de Zoeten EF. Collins CB, et al. J Crohns Colitis. 2018 Nov 28;12(12):1475-1485. doi: 10.1093/ecco-jcc/jjy105. J Crohns Colitis. 2018. PMID: 30085016 Free PMC article.

Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression - PubMed (original) (raw)