title: p53 in the Myeloid Lineage Modulates an Inflammatory Microenvironment Limiting Initiation and Invasion of Intestinal Tumors.
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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: He
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Chen-Xi
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Yin-Yin
authors.initials: YY
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China. Electronic address: liug53@nju.edu.cn.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019070:Cell Lineage; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055153:Stem Cell Niche; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53