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Repression of MUC2 gene expression by butyrate, a physiological regulator of intestinal cell maturation

Oncogene volume 22, pages 4983–4992 (2003)Cite this article

Abstract

Sodium butyrate (NaB) inhibits proliferation, stimulates apoptosis, and promotes differentiation of human colon cancer cells along the absorptive phenotype. In vitro, butyrate induces a switch from cells with a secretory to an absorptive phenotype. Here, we report that NaB specifically represses the expression of the MUC2 gene, a differentiation marker of the secretory goblet cell lineage, in forskolin- and 12-O-tetradecanoylphorbol 13-acetate-induced HT29 cells, and Cl.16E cells, a clonal derivative of HT29 cells that spontaneously differentiates into goblet cells. Thus, NaB repression is independent of the nature of the stimulus that triggers MUC2 expression. Further, repression was independent of new protein synthesis. Our results suggest that inhibition of MUC2 is linked to the ability of butyrate to repress histone deacetylase activity, since trichostatin A, another inhibitor of histone deacetylases, also inhibited MUC2 expression in induced HT29 cells. Finally, we demonstrate that the NaB effect is specific for this marker of the secretory cell lineage, since carcinoembryonic antigen, which is expressed in both the secretory and absorptive cells, is induced by NaB. Thus, the NaB repression of a definitive function of the secretory cell lineage is a further mechanism, in addition to the effects on proliferation and apoptotic pathways, through which butyrate can regulate intestinal homeostasis.

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Abbreviations

F:

forskolin

HDAC:

histone deacetylase

ITF:

intestinal trefoil factor

MEK-1:

mitogen-activated protein kinase kinase-1

NaB:

sodium butyrate

TSA:

trichostatin A

TPA:

12-O-tetradecanoylphorbol 13-acetate

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Acknowledgements

This work was supported in part by Grants CA-90808, CA-68965, and P30CA-13330. We thank Lidija Klampfer for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, 111 East 210th Street, Bronx, 10467, NY, USA

    Leonard Augenlicht, Li Shi, John Mariadason & Anna Velcich

  2. INSERM U539, Faculté de Médicine, 1 Rue Gaston Veil, Nantes, 44035, France

    Christian Laboisse

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  1. Leonard Augenlicht
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Correspondence to Anna Velcich.

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Augenlicht, L., Shi, L., Mariadason, J. et al. Repression of MUC2 gene expression by butyrate, a physiological regulator of intestinal cell maturation. Oncogene 22, 4983–4992 (2003). https://doi.org/10.1038/sj.onc.1206521

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