TY - JOUR
T1 - Repression of MUC2 gene expression by butyrate, a physiological regulator of intestinal cell maturation
AU - Augenlicht, Leonard
AU - Shi, Li
AU - Mariadason, John
AU - Laboisse, Christian
AU - Velcich, Anna
N1 - Funding Information:
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.
PY - 2003/8/7
Y1 - 2003/8/7
N2 - 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 C1.16E 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.
AB - 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 C1.16E 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.
KW - Goblet cell lineage
KW - Human MUC2 gene
KW - MUC2 expression
KW - Sodium butyrate and differentiation
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U2 - 10.1038/sj.onc.1206521
DO - 10.1038/sj.onc.1206521
M3 - Article
C2 - 12902981
AN - SCOPUS:0042284849
SN - 0950-9232
VL - 22
SP - 4983
EP - 4992
JO - Oncogene
JF - Oncogene
IS - 32
ER -