Dataset Information

?-Catenin and p120 mediate PPAR?-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia.

ABSTRACT: Colonization of gastric mucosa by Helicobacter pylori leads to epithelial hyperproliferation, which increases the risk for gastric adenocarcinoma. One H pylori virulence locus associated with cancer risk, cag, encodes a secretion system that transports effectors into host cells and leads to aberrant activation of ?-catenin and p120-catenin (p120). Peroxisome proliferator-activated receptor (PPAR)? is a ligand-activated transcription factor that affects oncogenesis in conjunction with ?-catenin. We used a carcinogenic H pylori strain to define the role of microbial virulence constituents and PPAR? in regulating epithelial responses that mediate development of adenocarcinoma.Gastric epithelial cells or colonies were co-cultured with the H pylori cag(+) strain 7.13 or cagE(-), cagA(-), soluble lytic transglycosylase(-), or cagA(-)/soluble lytic transglycosylase(-) mutants. Levels of PPAR? and cyclin E1 were determined by real-time, reverse-transcription polymerase chain reaction, immunoblot analysis, or immunofluorescence microscopy; proliferation was measured in 3-dimensional culture. PPAR? and Ki67 expression were determined by immunohistochemical analysis of human biopsies and rodent gastric mucosa.H pylori induced ?-catenin- and p120-dependent expression and activation of PPAR? in gastric epithelial cells, which were mediated by the cag secretion system substrates CagA and peptidoglycan. H pylori stimulated proliferation in vitro, which required PPAR?-mediated activation of cyclin E1; H pylori did not induce expression of cyclin E1 in a genetic model of PPAR? deficiency. PPAR? expression and proliferation in rodent and human gastric tissue was selectively induced by cag(+) strains and PPAR? levels normalized after eradication of H pylori.The H pylori cag secretion system activates ?-catenin, p120, and PPAR?, which promote gastric epithelial cell proliferation via activation of cyclin E1. PPAR? might contribute to gastric adenocarcinoma development in humans.

SUBMITTER: Nagy TA

PROVIDER: S-EPMC3152603 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

β-Catenin and p120 mediate PPARδ-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia.

Nagy Toni A TA Wroblewski Lydia E LE Wang Dingzhi D Piazuelo M Blanca MB Delgado Alberto A Romero-Gallo Judith J Noto Jennifer J Israel Dawn A DA Ogden Seth R SR Correa Pelayo P Cover Timothy L TL Peek Richard M RM

Gastroenterology 20110517 2

<h4>Background & aims</h4>Colonization of gastric mucosa by Helicobacter pylori leads to epithelial hyperproliferation, which increases the risk for gastric adenocarcinoma. One H pylori virulence locus associated with cancer risk, cag, encodes a secretion system that transports effectors into host cells and leads to aberrant activation of β-catenin and p120-catenin (p120). Peroxisome proliferator-activated receptor (PPAR)δ is a ligand-activated transcription factor that affects oncogenesis in co ...[more]

PMID: 21704622

Similar Datasets

Project description:Background: Negative-pressure wound therapy has become widely available in modern chronic wound cares. Accelerated keratinocyte (HaCaT cell) movements and decreased E-cadherin expressions induced by the applied negative pressure gradient of 125 mmHg (NP) have been reported in previous studies. However, the molecular mechanism for E-cadherin regulations under NP remains unexplored. We highlighted the signal transduction involved in NP-induced E-cadherin regulation for keratinocytes in the study. Results: Microarray results showed that catenin 1 (CTNND1) gene, the gene encoding the p120-catenin (p120ctn) in cell-cell junctions, was significantly (p = 0.0005) upregulated in HaCaT cells under NP for 12 hours in comparison with those at ambient pressure (AP). Cell fractionations and immunoblotting data showed that NP increased p120ctn phosphorylation, and resulted in p120ctn translocation from the plasma membrane to the cytoplasm. Fluorescent stains suggested that NP diminished the co-localization of p120ctn and E-cadherin on the plasma membrane. Similar phenomenon was also observed in the cells with overexpressed p120ctn at NP. Interestingly, overexpression of dN- p120ctn, a deletion mutant of p120ctn without the N-terminal phosphorylation sites, restored the adherens junctions (AJ) at NP. Knockdown of p120ctn with lentiviral small hairpin RNA not only diminished E-cadherin expressions but also accelerated cell movement at AP. Conclusions: Phosphorylation of p120ctn is endowed to respond rapidly to NP and contributes to the AJ disassembly. This NP-induced E-cadherin downregulation can possibly accelerate wound-healing process. Conclusions: Phosphorylation of p120ctn is endowed to respond rapidly to NP and contributes to the AJ disassembly. This NP-induced E-cadherin downregulation can possibly accelerate wound-healing process. HaCaT cells under negative pressure (NP) gradient of 125 mmHg for 12 hours in comparison with those at ambient pressure (AP) were tested for RNA extraction and hybridization on Affymetrix microarrays. The experiments have been biological replicated three times. The differential expression gene between NP and AP were selected and validated with qPCR method.

Dataset Information

?-Catenin and p120 mediate PPAR?-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia.

Publications

β-Catenin and p120 mediate PPARδ-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets