Reference SummaryHe XY, Cell Rep 2015 Nov 3;13(5):888-97

Title

 p53 in the Myeloid Lineage Modulates an Inflammatory Microenvironment Limiting Initiation and Invasion of Intestinal Tumors.

Authors

 He XY; Xiang C; Zhang CX; Xie YY; Chen L; Zhang GX; Lu Y; Liu G

Journal

 Cell Rep

Volume

 13

Issue

 5

Year

 2015

Pages

 888-97

Abstract

 Chronic inflammation promotes the development and progression of various epithelial tumors. Wild-type p53 suppresses inflammation, but it is unclear whether the role of p53 in suppression of inflammation is linked to its tumor suppression function. Here, we established mouse models of myeloid lineage-specific p53 deletion or activation to examine its role in inflammation-related intestinal tumorigenesis. Impaired p53 in the myeloid linage resulted in elevated levels of inflammatory mediators and stimulated adenoma initiation in Apc(Min/+) mice. In contrast, mice with mild p53 activation in the myeloid lineage attenuated the inflammatory response and were more resistant to intestinal tumor development and invasion, which were initiated through Apc(Min/+) mutation or carcinogen and promoted by colitis. Furthermore, p53 activation also suppressed alternative (M2) macrophage polarization together with c-MYC downregulation. Therefore, as a regulator of macrophage function, p53 is critical to protection against tumorigenesis in a non-cell-autonomous manner.

Links

 J:228954 – MGI References
26565902 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon - Distal tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon - Distal

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon - Distal tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon - Distal

observed
FVB.B6-Mdm2tm2.1Glo/+ Intestine - Large Intestine - Colon adenocarcinoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon adenocarcinoma
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

0
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon adenocarcinoma
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon adenocarcinoma
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
FVB.B6-Mdm2tm2.1Glo/+ Intestine - Large Intestine - Colon dysplasia - high grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon dysplasia - high grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed
FVB.B6-Mdm2tm2.1Glo/+ Intestine - Large Intestine - Colon dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon polyp Intestine - Large Intestine - Colon

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon polyp Intestine - Large Intestine - Colon

observed
FVB.B6-Mdm2tm2.1Glo/+ Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

34
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

34
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine - Colon

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine adenocarcinoma
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine

0
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine adenocarcinoma
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine

66.67
FVB.B6-Mdm2tm2.1Glo/+ Intestine - Large Intestine tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine

observed
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Large Intestine tumor
  • dextran sulfate sodium (DSS)
 Intestine - Large Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine - Distal adenoma Intestine - Small Intestine - Distal

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine - Small Intestine - Distal polyp Intestine - Small Intestine - Distal

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine - Distal polyp Intestine - Small Intestine - Distal

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine - Small Intestine - Medial polyp Intestine - Small Intestine - Medial

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine - Proximal adenoma Intestine - Small Intestine - Proximal

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine - Small Intestine - Proximal polyp Intestine - Small Intestine - Proximal

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine - Proximal polyp Intestine - Small Intestine - Proximal

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn Intestine - Small Intestine adenoma Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn Intestine - Small Intestine tumor Intestine - Small Intestine

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

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine adenoma Intestine

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine adenoma Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine adenoma Intestine

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine adenoma Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine adenoma - microadenoma Intestine

observed - 100
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine adenoma - microadenoma Intestine

observed - 100
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine adenoma - microadenoma Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine adenoma - microadenoma Intestine

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

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine polyp Intestine

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine polyp Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Gt(ROSA)26Sortm1Sor Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine polyp Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo Trp53tm1Brn/+ Intestine tumor Intestine

observed
C57BL/6-ApcMin/+ Trp53tm1Brn/+ Intestine tumor Intestine

observed
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine tumor Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Intestine tumor Intestine

observed
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Gt(ROSA)26Sortm1Sor Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ Leukocyte - Myelocyte (Granulocyte) tumor Intestine

observed
C57BL/6-Lyz2tm1(cre)Ifo/+ Trp53tm1Brn (Unspecified organ) tumor (Unspecified organ)

0
C57BL/6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ (Unspecified organ) tumor (Unspecified organ)

0