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 |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon - Distal tumor |
|
Intestine - Large Intestine - Colon - Distal |
observed |
|
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon - Distal tumor |
|
Intestine - Large Intestine - Colon - Distal |
observed |
|
FVB.B6-Mdm2tm2.1Glo/+ | Intestine - Large Intestine - Colon adenocarcinoma |
|
Intestine - Large Intestine - Colon |
observed |
|
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon adenocarcinoma |
|
Intestine - Large Intestine - Colon |
0 |
|
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon adenocarcinoma |
|
Intestine - Large Intestine - Colon |
observed |
|
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon adenocarcinoma |
|
Intestine - Large Intestine - Colon |
observed |
|
FVB.B6-Mdm2tm2.1Glo/+ | Intestine - Large Intestine - Colon dysplasia - high grade |
|
Intestine - Large Intestine - Colon |
observed |
|
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon dysplasia - high grade |
|
Intestine - Large Intestine - Colon |
observed |
|
FVB.B6-Mdm2tm2.1Glo/+ | Intestine - Large Intestine - Colon dysplasia - low grade |
|
Intestine - Large Intestine - Colon |
observed |
|
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon dysplasia - low grade |
|
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 |
|
Intestine - Large Intestine - Colon |
34 |
|
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
34 |
|
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
observed |
|
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
observed |
|
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine adenocarcinoma |
|
Intestine - Large Intestine |
0 |
|
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine adenocarcinoma |
|
Intestine - Large Intestine |
66.67 |
|
FVB.B6-Mdm2tm2.1Glo/+ | Intestine - Large Intestine tumor |
|
Intestine - Large Intestine |
observed |
|
FVB.B6-Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine tumor |
|
Intestine - Large Intestine |
observed |
|
C57BL/6-ApcMin/+ Lyz2tm1(cre)Ifo/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine tumor |
|
Intestine - Large Intestine |
observed |
|
C57BL/6-ApcMin/+ Mdm2tm2.1Glo/+ Mdm4tm1Glo/+ | Intestine - Large Intestine tumor |
|
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 |