Gastric Mucosa Abnormalities and Tumorigenesis in Mice Lacking the pS2 Trefoil Protein

Lefèbvre, Olivier; Chenard, Marie–Pierre; Masson, Régis; Linares, José Luis; Dierich, Andrée; LeMeur, Marianne; Wendling, Corinne; Tomasetto, Catherine; Chambon, Pierre; Rio, Marie‐Christine

doi:10.1126/science.274.5285.259

Cited by 471 publications

(440 citation statements)

References 27 publications

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“…One of them, TFF2, is a member of the trefoil family of peptides, which displays a wellestablished protective effect of the gastrointestinal tract by promoting the healing of injured mucosa (Farrell et al, 2002). TFF2 and the other member of the family, TFF1, have been reported to be frequently downregulated in primary gastric cancers (Kirikoshi and Katoh, 2002;Kim et al, 2003), and TFF1 might be a gastric-specific tumor suppressor gene (Lefebvre et al, 1996). Other two epithelial-specific genes, downregulated in AGC, are those encoding claudin 18 and 23.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of early and advanced gastric cancers

et al. 2007

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Gastric carcinoma is one of the major causes of cancer mortality worldwide. Early detection results in excellent prognosis for patients with early cancer (EGC), whereas the prognosis of advanced cancer (AGC) patients remains poor. It is not clear whether EGC and AGC are molecularly distinct, and whether they represent progressive stages of the same tumor or different entities ab initio. Gene expression profiles of EGC and AGC were determined by Affymetrix technology and quantitative polymerase chain reaction. Representative regulated genes were further analysed by in situ hybridization (ISH) on tissue microarrays. Expression analysis allowed the identification of a signature that differentiates AGC from EGC. In addition, comparison with normal gastric mucosa indicated that the majority of alterations associated with EGC are retained in AGC, and that further expression changes mark the transition from EGC to AGC. Finally, ISH analysis showed that representative genes, differentially expressed in the invasive areas of EGC and AGC, are not differentially expressed in the non-invasive areas of the same tumors. Our data are more directly compatible with a progression model of gastric carcinogenesis, whereby EGC and AGC may represent different molecular stages of the same tumor. Finally, the identification of an AGC-specific signature might help devising novel therapeutic strategies for advanced gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis of early and advanced gastric cancers

et al. 2007

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“…Some putative tumor suppressor genes or genes with known growth inhibitory effects in the gastrointestinal tract can also be found in this cluster. These include TFF1-mice lacking TFF1 develop gastric adenomas and intramucosal carcinomas (Lefebvre et al, 1996)-and CDKN1C, the gene encoding the p57KIP2 cyclin-dependent kinase inhibitor, whose promoter has been found to be methylated, accompanied by transcriptional silencing, in some gastric cancer cell lines (Shin et al, 2000).…”

Section: Heterogeneity Of the Gene Expression Patterns Among Gastric mentioning

confidence: 99%

Variation in Gene Expression Patterns in Human Gastric Cancers

Chen

Leung

Yuen

et al. 2003

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Gastric cancer is the world's second most common cause of cancer death. We analyzed gene expression patterns in 90 primary gastric cancers, 14 metastatic gastric cancers, and 22 nonneoplastic gastric tissues, using cDNA microarrays representing ∼30,300 genes. Gastric cancers were distinguished from nonneoplastic gastric tissues by characteristic differences in their gene expression patterns. We found a diversity of gene expression patterns in gastric cancer, reflecting variation in intrinsic properties of tumor and normal cells and variation in the cellular composition of these complex tissues. We identified several genes whose expression levels were significantly correlated with patient survival. The variations in gene expression patterns among cancers in different patients suggest differences in pathogenetic pathways and potential therapeutic strategies

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“…TFF1 protects injured gastric mucosal epithelial cells (Kindon et al, 1995;Tomasetto et al, 2000) and accordingly gastric TFF1-deficient mice develop antro-pyloric adenomas and carcinomas. Thus, TFF1 is a candidate gastric-specific tumor suppressor to protect the mucosa against acid, digestive enzymes and pathogens, such as Helicobacter pylori (Rio et al, 1988;Lefebvre et al, 1996;Van De Bovenkamp et al, 2005). In contrast, TFF1 is absent in normal colon but is induced at high levels in Crohn disease and colorectal cancers (Emami et al, 2004).…”

Section: Introductionmentioning

confidence: 99%