Aspirin promotes TFF2 gene activation in human gastric cancer cell lines

Azarschab, Pia; Al-azzeh, Ezzal-din; Kornberger, Wolfgang; Gött, Peter

doi:10.1016/s0014-5793(00)02422-4

Cited by 25 publications

(14 citation statements)

References 32 publications

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“…These results are in line with studies showing that Tff3-null mice challenged with 2.5% of DSS have impaired mucosal healing and are more sensitive to the injurious effects of DSS than the wild type (7). Also, both in vitro and in vivo studies have shown that PPARg ligands such as troglitazone and prostaglandins, and nonsteroidal antiinflammatory drugs such as aspirin upregulate TFF2 expression (19,48,49), which leads to inhibition of DSS-induced colitis and azoxymethane-induced colon carcinoma (50). No evidence of TFF3 regulation by PPARg has been indicated, making this study the first one to our knowledge suggesting this link.…”

Section: Discussionsupporting

confidence: 88%

Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Borniquel

Jädert

Lundberg

2012

The Journal of Nutrition

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A central event in inflammatory bowel disease is the disruption of the mucosal homeostasis. Trefoil peptides [(TFF)] are emerging as key mediators in the defense and repair of the gastrointestinal mucosa. Here, we demonstrate induction of TFF by CLA with therapeutic antiinflammatory effects in a mouse model of inflammatory bowel disease. SW480 cells were treated with linoleic acid or CLA (0-2.5 μmol/L) in the absence or presence of the PPARγ inhibitor GW9662. Cells treated with CLA showed an upregulation of the intestinal trefoil factor, which was prevented by pretreatment with GW9662. Dextran sulfate sodium (2%) was used to induce colitis in mice and they were simultaneously fed with a standard or a CLA-supplemented (100 mg · kg(-1) · d(-1)) diet for 7 d. The CLA-enriched diet prevented the colon shortening induced by DSS and markedly reduced the disease activity index and the colonic expression of inducible NO synthase and NF-κB. Immunohistochemistry revealed an increase in PPARγ and TFF3 expression after CLA administration. Altogether, these results indicate that dietary CLA protects against DSS-induced colitis in a process involving induction of PPARγ and TFF3.

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Section: Discussionsupporting

confidence: 88%

Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Borniquel

Jädert

Lundberg

2012

The Journal of Nutrition

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“…Approximately 30% of TFF1 knockout mice develop gastric adenomas and carcinomas (25), and occasional mutations, allelic deletions, and reduced expression occur in human primary GCs (12,33). Importantly, TFF1 and TFF2 (1) are upregulated by the CRC prevention agents, nonsteroidal anti-inflammatory drugs, indomethacin, and aspirin (2). We found that TFF-1 to -3, while not expressed in normal lymphocytes, were all expressed in normal colon but that TFF1 expression was absent from four, TFF2 was absent from three, and TFF3 was absent from three of seven cancer cell lines (Table 1 and Fig.…”

Section: Resultsmentioning

confidence: 99%

GATA-4 and GATA-5 Transcription Factor Genes and Potential Downstream Antitumor Target Genes Are Epigenetically Silenced in Colorectal and Gastric Cancer

Akiyama

Watkins

Suzuki

et al. 2003

Molecular and Cellular Biology

237

193

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The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in embryonic and adult settings. We now show that in colorectal cancer (CRC) and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 but are never seen for GATA-6. Potential antitumor target genes upregulated by GATA-4 and -5, the trefoil factors, inhibin␣, and disabled-2 (Dab2) are also silenced, in GI cancers, with associated methylation of the promoters. Drug or genetically induced demethylation simultaneously leads to expression, in CRC cells, of all of the GATA-4, -5, and downstream genes. Expression of exogenous GATA-5 overrides methylation at the downstream promoters to activate the target genes. Selection for silencing of both upstream transcription factors and their target genes in GI cancers could indicate that epigenetic silencing of the involved genes provides a summated contribution to tumor progression.

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“…Therefore, although possibility of the involvement of other signaling pathways is not completely excluded, we hypothesize that PPARγ mainly mediates the action of aspirin on TFF2 expression. Azarschab et al [15] mapped an aspirin responding element to −546 to −758 bp upstream of the TATA box of the human TFF2 gene. Since apparent PPRE is not present in the 5′‐flanking region of the human TFF2 gene, the effect of PPARγ may be indirect.…”

Section: Discussionmentioning

confidence: 99%

PPARγ mediates NSAIDs‐induced upregulation of TFF2 expression in gastric epithelial cells

et al. 2004

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Trefoil factor family (TFF) is a group of peptides that play critical roles in maintaining gastric mucosal integrity. In real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and reporter gene assays, we show that indomethacin and aspirin upregulate TFF2 expression in MKN45 gastric cells. These drugs also activated peroxisome proliferator-activated receptor Q Q (PPARQ Q) at concentration ranges that increase TFF2 expression, and upregulated TFF2 expression was suppressed by GW9662, a speci¢c inhibitor of PPARQ Q. These results suggest that indomethacin and aspirin upregulate gastric expression of TFF2 through activation of PPARQ Q. This mechanism may be important in reducing the extent of gastric mucosal injury caused by the administration of non-steroidal anti-in£ammatory drugs (NSAIDs).

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Aspirin promotes TFF2 gene activation in human gastric cancer cell lines

Cited by 25 publications

References 32 publications

Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

GATA-4 and GATA-5 Transcription Factor Genes and Potential Downstream Antitumor Target Genes Are Epigenetically Silenced in Colorectal and Gastric Cancer

PPARγ mediates NSAIDs‐induced upregulation of TFF2 expression in gastric epithelial cells

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