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 |
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 |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
[not specified]-Cebpatm1Gonz | Intestine - Large Intestine - Colon - Distal adenoma |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr | Intestine - Large Intestine - Colon - Distal dysplasia - low grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
[not specified]-Cebpatm1Gonz | Intestine - Large Intestine - Colon - Distal dysplasia - low grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
observed |
|
[not specified]-Cebpatm1Gonz | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
observed |
|
[not specified]-Cebpatm1Gonz Tg(Vil1-cre/ERT2)23Syr | Intestine - Large Intestine - Colon lesion |
|
Intestine - Large Intestine - Colon |
observed |
|
[not specified]-Cebpatm1Gonz | Intestine - Large Intestine - Colon lesion |
|
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 |