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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Loss of p53 in enterocytes facilitates an inflammatory microenvironment enabling invasion and metastasis of carcinogen-induced colorectal tumors

ABSTRACT: Here, we examined the role of intestinal epithelial specific tumor suppressive function of 53. We provide evidence that p53 plays a dual role during carcinogen-induced tumorigenesis. At the initiation stage, p53 controls DNA damage and survival of initiated epithelia. In contrast, at later stages, loss of p53 is associated with the formation of an inflammatory microenvironment that is linked to epithelial mesenchymal transition, invasion and metastasis and the activation of NF-kappaB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function during the progression stage of colorectal cancer that is independent of its well-established role in cell cycle regulation, apoptosis and senescence. 6 samples were analyzed. We compared 3 wt colon tumor samples and 3 p53-knockout tumor samples.

ORGANISM(S): Mus musculus

SUBMITTER: Olivia Prazeres da Costa

PROVIDER: E-GEOD-27868 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and metastasis of carcinogen-induced colorectal tumors

Project description:Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC) specific deletion of p53, we demonstrate that single loss of p53 is not sufficient to initiate intestinal tumorigenesis, but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. While during the initiation stage p53 controls DNA damage and IEC survival, during tumor progression, loss of p53 is associated with the formation of an inflammatory microenvironment and activation of NF-kB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function that is independent of its well-established role in cell cycle regulation, apoptosis and senescence. 4 AOM induced cancers derived from Tp53DEIC mice were isolated and DNA was extracted. These were compared to genomic DNA isolated from healthy littermate control animals. Agilent Mouse 4x180K arrays were used (Design ID 27411).

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Loss of p53 in enterocytes facilitates an inflammatory microenvironment enabling invasion and metastasis of carcinogen-induced colorectal tumors

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Mus musculus

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