Reference SummaryHeuberger J, Life Sci Alliance 2019 Feb;2(1):e201800173

Title

 A C/EBPalpha-Wnt connection in gut homeostasis and carcinogenesis.

Authors

 Heuberger J; Hill U; Forster S; Zimmermann K; Malchin V; Kuhl AA; Stein U; Vieth M; Birchmeier W; Leutz A

Journal

 Life Sci Alliance

Volume

 2

Issue

 1

Year

 2019

Pages

 e201800173

Abstract

 We explored the connection between C/EBPalpha (CCAAT/enhancer-binding protein alpha) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPalpha was expressed in human and murine intestinal epithelia in the transit-amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APC(Min/+) polyps, C/EBPalpha was absent in the nuclear beta-catenin-positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPalpha KO in murine gut epithelia increased tumor volume. C/EBPalpha deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of beta-catenin in organoids attenuated C/EBPalpha expression, and ectopic C/EBPalpha expression in HCT116 cells abrogated proliferation. C/EBPalpha expression accompanied differentiation of the colon cancer cell line Caco-2, whereas beta-catenin stabilization suppressed C/EBPalpha. These data suggest homeostatic and oncogenic suppressor functions of C/EBPalpha in the gut by restricting Wnt signaling.

Links

 J:285503 – MGI References
30599048 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr Intestine - Large Intestine - Colon - Distal adenoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

100
[not specified]-Cebpatm1Gonz Intestine - Large Intestine - Colon - Distal adenoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

100
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr Intestine - Large Intestine - Colon - Distal dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

100
[not specified]-Cebpatm1Gonz Intestine - Large Intestine - Colon - Distal dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

100
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr Intestine - Large Intestine - Colon adenoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Cebpatm1Gonz Intestine - Large Intestine - Colon adenoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr Intestine - Large Intestine - Colon lesion
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Cebpatm1Gonz Intestine - Large Intestine - Colon lesion
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
C57BL/6J-ApcMin/+ Intestine adenoma Intestine

observed
C57BL/6J-ApcMin/+ Intestine polyp Intestine

observed
C57BL/6J-ApcMin/+ Intestine tumor Intestine

observed