Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trefoil peptides are small secretory proteins characterized by three intrachain disulfide bonds forming the trefoil motif or P-domain. They are abundantly expressed on mucosal surfaces, especially of the gastrointestinal tract. In pathological conditions such as ulcers, metaplasia and neoplasia, their expression is upregulated. Three human trefoil peptides have been described: the estrogen-inducible pS2 protein, the spasmolytic protein and the intestinal trefoil factor. Recently, their role in the maintenance of surface integrity and ulcer healing was discussed. We already mapped the corresponding three genes (BCEI), SML1, TFF3) to the same genomic region (21q22.3). In this paper, we show that the three genes are clustered in a tandemly orientated fashion within 50 kb on a bacterial artificial chromosome (BAC) recombinant. This cluster is located adjacent to D21S19 and the locus order is cen-D21S212-TFF3-SML1-BCEI-D21S19-tel, whereas transcription of all three genes is directed towards the centromere. The gene structure of SML1 exhibits four exons, two of which encode the two separate trefoil motifs. TFF3 and BCEI, both containing one trefoil motif, are composed of three exons each, suggesting gene duplication and exon-shuffling events during evolution. The 5'-flanking region of SML1 was compared to the corresponding region of other trefoil genes. Two motifs with identical sequence and positions are shared between SML1 and BCEI, thus presenting possible targets for stomach-specific gene regulation. Two other motifs are shared within all known human and rat trefoil genes, suggesting a coordinated regulation and/or a common locus-controlling region. Using RT-PCR, a change in the pattern of trefoil gene expression is detected in tissue samples from normal gastric mucosa, hyperplastic polyps, gastric cancer, and gastric cancer cell lines, respectively.
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PMID:Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression. 904 62

Peptides belonging to the trefoil factor family (TFF) protect the gastrointestinal epithelia. Overexpression of TFFs was observed in pathological conditions such as gastritis, ulceration, metaplasia and neoplasia of the gastrointestinal tract. The aims of this work were to investigate the recently described TFF2 gene polymorphism in different European populations. DNA samples from blood of healthy individuals and gastric cancer patients were genotyped using the polymerase chain reaction. They were compared to a gastric cancer population. The results do not show any significant difference in allelic frequencies between gastric cancer patients and healthy individuals from Portugal. However, the frequency of the two alleles found varies considerably among Europeans.
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PMID:Variable distribution of TFF2 (Spasmolysin) alleles in Europeans does not indicate predisposition to gastric cancer. 985 57

Metaplastic cell lineages arising in response to chronic injury are precursors for the evolution of dysplasia and adenocarcinoma. Although a subtype of intestinal metaplasia has been associated with gastric adenocarcinoma, the link between this lineage and the evolution of gastric adenocarcinoma has remained unclear. Wang et al (1998) have reported that an aberrant metaplastic cell lineage with morphological characteristics similar to Brunner's glands of the duodenum develops in the fundic mucosa of mice infected with Helicobacter felis. This metaplastic lineage expresses the trefoil peptide spasmolytic polypeptide (SP). Given the epidemiological association of Helicobacter species infection with gastric cancer, we hypothesized that this SP-expressing metaplastic (SPEM) lineage may represent a precursor to or appear commensurate with gastric adenocarcinoma. The SPEM lineage was present in 68% of fundic biopsies from patients with fundic Helicobacterpylori-associated gastritis, but was absent in biopsies of fundic mucosa from patients without H. pylori infection. In a review of archival samples from 22 resected gastric adenocarcinomas, we found the SPEM lineage in 91% of cases, typically located in mucosa adjacent to the carcinoma or areas of dysplasia. Importantly, 59% of resections showed SP immunoreactivity within dysplastic cells. These data indicate a strong association of the SPEM lineage with both chronic H. pylori infection and gastric adenocarcinoma.
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PMID:Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. 1037 6

Expression of some members of the trefoil factor (TFF) and the WNT gene families is regulated together by estrogen. We have cloned and characterized human WNT signaling molecules using bioinformatics, cDNA-library screening and cDNA-PCR to investigate expression profile of WNT signaling molecules in human gastric cancer. Here, we investigated expression profile of TFF1/pS2, TFF2/SP and TFF3/ITF in human gastric cancer. Among 7 gastric cancer cell lines, TFF1 was expressed in OKAJIMA, TMK1, MKN45, and KATO-III, TFF2 in KATO-III, and TFF3 in MKN45 and KATO-III. TFFs were preferentially expressed in diffuse-type gastric cancer cell lines. Expression of TFFs in primary gastric cancer was next investigated. TFF1 was down-regulated in 7 cases out of 12 cases (58.3%) of primary gastric cancer. TFF2 was down-regulated in 10 out of 12 cases (83.3%) of primary gastric cancer. TFF3 was down-regulated in 2 out of 12 cases (16.7%) of primary gastric cancer, and was up-regulated in 5 out of 12 cases (41.7%). TFF1 and TFF2 were frequently down-regulated in primary gastric cancer, while TFF3 was up-regulated in some cases of primary gastric cancer. This is the first report on comprehensive expression analyses on TFFs in gastric cancer.
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PMID:Expression of TFF1, TFF2 and TFF3 in gastric cancer. 1216 14

Trefoil factor family (TFF) domain peptides consist of three members that play a role in intestinal mucosal defence and repair, and in tumourigenesis. The role of the three TFF members in the gastric carcinogenesis cascade remains poorly defined. This study examined seven gastric cell lines, 50 gastric cancers and their adjacent non-cancer tissues, and tissues from 40 non-cancer patients, in order to elucidate the chronology of TFF expression in various stages of gastric carcinogenesis. TFF expression was determined by RT-PCR, immunohistochemistry, and western blot. Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines. Specifically, TFF1 was detected in all non-cancer patients, but was detected in only 50% of gastric cancer and 66% of adjacent normal tissues. TFF2 expression was demonstrated in 87.5% of non-cancer patients, 34% of gastric carcinomas, and 58% of adjacent non-cancer tissues. There was a significant correlation between TFF1 and TFF2 expression in gastric cancer and adjacent non-cancer tissues (p<0.001). By contrast, TFF3 was detected in 25% of non-cancer patients and showed a predilection for areas with intestinal metaplasia (p=0.005). Sixty-two per cent of gastric cancers and 24% of neighbouring non-cancer tissues showed TFF3 expression. Immunoreactivity against TFF3 was demonstrated in goblet cells of intestinal metaplasia and within the cytoplasm and nuclei of tumour cells. Progressive loss of TFF1 and TFF2, together with the induction of TFF3, is likely to be involved in the early stage of the multi-step gastric carcinogenesis pathway.
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PMID:Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. 1221 76

Recent studies have described a spasmolytic polypeptide-expressing metaplastic cell lineage (SPEM) in the gastric fundic mucosa associated with both chronic H. pylori infection and gastric adenocarcinoma. We investigated the association of SPEM both with early gastric adenocarcinoma and in biopsies taken from patients prior to diagnosis of cancer. Two cohorts were examined. First, gastric resections from 29 patients with early gastric cancer were examined. Second, biopsies taken from 18 patients prior to the diagnosis of gastric cancer were compared with their respective resection specimens as well as with control biopsies from a cohort of 19 patients diagnosed with gastritis without subsequent development of cancer. The presence of SPEM and intestinal metaplasia (IM) adjacent to and distant from the cancer was compared and spasmolytic polypeptide (SP) immunostaining within dysplastic/cancerous cells was identified. SPEM was present adjacent to cancer in all early cancer cases where the tumor was located in the body or at the body/antrum junction, and was present in the body mucosa distant from the cancer in 76% of cases. Intestinal metaplasia was found adjacent to the tumor in 76% of cases and in body sections in 52% of resections. SP immunostaining was noted within cancer cells in 62% of tumors, and within dysplastic cells in 76% of resections where dysplasia was present. SPEM was present in 82% of the biopsies obtained prior to the diagnosis of cancer, compared with only 37% in the gastritis cohort. IM was present in only 57% of biopsies. In conclusion, SPEM is strongly associated with early gastric cancers and is observed in gastric biopsies prior to the development of cancer. In addition, early gastric cancers demonstrated a high incidence of SP expression. These results suggest that SPEM merits consideration as an important pre-neoplastic gastric lesion.
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PMID:Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland. 1275 53

TFF1/pS2, TFF2/SP and TFF3/ITF are soluble peptides with trefoil domain(s) and C-terminal dimerization domain, which are conserved among human, cow, mouse and rat. TFF1 mRNA is expressed in stomach (mucous cells in fundus and antrum), TFF2 mRNA in stomach (mucous neck cells in fundus and basal cells in antral and pyloric glands) and duodenum (Brunner's gland), TFF3 mRNA in small intestine and large intestine (goblet cells). Expression of TFF1, TFF2 and TFF3 mRNAs are differentially regulated by FGF2/bFGF, FGF7/KGF, estrogen, aspirin, arachidonic acid, X-ray irradiation, and hydrogen peroxide. Gastric cancer is classified into the intestinal type and the diffuse type. TFF mRNAs are preferentially expressed in diffuse-type gastric cancer cells. Custom-made microarray (TFF mRNAs) and ELISA (TFF proteins) might be applicable for screening methods of peritoneal and bone marrow dissemination from diffuse-type gastric cancer. TFF1 and TFF2 mRNAs are frequently down-regulated in intestinal-type gastric cancer. TFF1 gene, inactivated by deletion, missense mutation and promoter hypermethylation, is a tumor suppressor gene implicated in gastric cancer. TFF2 is a candidate tumor suppressor gene; however, genetic and epigenetic alterations of TFF2 gene in human gastric cancer remain unclear. TFF1, TFF2 and TFF3 play key roles in mucosal protection through mucous-barrier formation, and also in mucosal repair through promotion of restitution after injury. Patients with chronic atrophic gastritis and those with ulcerative colitis are at risk of gastric cancer and colorectal cancer, respectively. TFF1, TFF2 and TFF3 proteins might be applicable for chemoprevention of gastrointestinal cancer associated with chronic persistent inflammation.
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PMID:Trefoil factors and human gastric cancer (review). 1279 1

Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer treatment because advanced gastric cancer often turns out incurable with peritoneal metastasis. Molecular detection of minimal cancer cells from peritoneal washings may overcome the sensitivity boundary of conventional cytology and contribute to the prediction of the disease outcome. To select marker candidates out of ten thousands of genes, we performed microarray analyses in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40 candidates selected by the above expression profiling, RT-PCR in 16 representative peritoneal wash samples was performed to identify genes specific to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2, TFF1, and TFF2, were then evaluated for their utility as a marker for minimal residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five genes showed positive results highly specific to incurable cases (91-100%). With a high specificity, the combination of these five genes succeeded in identifying 6 out of 20 (30%) additional patients with all types of early recurrence that could not be predicted by the conventional method. The six newly identified recurrences included four non-peritoneal ones, showing that RT-PCR using the five genes without a real-time quantitative PCR technique contributes to the detection of minimal residual disease.
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PMID:Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings. 1470 32

Trefoil factors family 2 (TFF2), also known as spasmolytic polypeptide, is primarily expressed in the mucus neck cells of gastrointestinal tracts. It has been proposed that TFF2 plays an important physiological role in protection, repair, and healing of gastrointestinal mucosa. To investigate the cis-acting regulatory element that control TFF2 tissue-specific expression, we studied the basal TFF2 promoter activity through transient transfection in several human cancer cell lines. Expression of TFF2 was found to be significantly greater in human breast cancer MCF-7 cells compared to other cancer cells. Results from TFF2 promoter luciferase reporter constructs revealed that the basal level of TFF2 promoter activity was overall more than two-fold higher in MCF-7 cells compared to that of other cell lines examined. Using EMSA assays and site-directed mutagenesis, we identified a cell line-specific transcriptional regulation element located in the TFF2 promoter 5'-flank sequence at -32/-27, and which contains a CCAAT/enhance binding proteins (C/EBPs) consensus-binding site. Mutation of this consensus site reduced the basal promoter activity by more than 50% in MCF-7 cells but had no effect in human gastric cancer cells. In conclusion, we have identified a CCAAT sequence as a cell line-specific cis-acting regulatory element that may contribute to the high level expression of TFF2 in MCF-7 cells. These results also suggest the possibility that TFF2 could play a role in mammary gland tumorigenesis.
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PMID:Characterization of a CCAAT-enhancer element of trefoil factor family 2 (TFF2) promoter in MCF-7 cells. 1517 80

Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (G-/-) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not G-/- stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the G-/- model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNgamma) was the most abundant proinflammatory cytokine in the G-/- stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both G-/- and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNgamma induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNgamma, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.
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PMID:Interferon gamma induction of gastric mucous neck cell hypertrophy. 1576 19


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