Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duodenal carcinomas, such as ampullary tumors, may be a heterogeneous group of neoplasms that share differentiation features with gastric or colorectal carcinomas. Because of the cell- and tissue-specific expression patterns of mucins and trefoil peptides, these markers were used to investigate the differentiation status of duodenal and ampullary carcinomas in comparison with gastric and colorectal carcinomas. Adenocarcinomas (14 duodenal, 10 gastric, 11 ampullary and 10 colorectal) were examined immunohistochemically for the mucin gene products MUC1, MUC2, MUC5AC, MUC6 and the trefoil peptides TFF1 and TFF2. The tumors' expression profile for MUC5AC, MUC6 and TFF1 was used to distinguish between gastric- and intestinal-directed differentiation. The mucins that were most often expressed in the individual tumor types were MUC1 (duodenal and ampullary carcinomas), MUC2 (colorectal carcinomas) and MUC5AC (gastric carcinomas). Further classification focusing on the expression profile for MUC5AC, MUC6 and TFF1 revealed that 21% of the duodenal and 45% of the ampullary carcinomas demonstrated mainly gastric differentiation (positivity for all three markers or only two of them). The remaining duodenal and ampullary carcinomas showed nongastric, i.e., intestinal differentiation (all three markers negative or only one marker positive). The gastric differentiation pattern characterized 60% of gastric carcinomas. Colorectal carcinomas showed intestinal differentiation in 100% of cases. Duodenal carcinomas have a heterogeneous mucin expression pattern that is mainly related to either gastric differentiation or intestinal differentiation. This also holds for ampullary carcinomas. Among the markers used, MUC5AC, MUC6 and TFF1 are most useful for revealing differentiation pathways in duodenal and ampullary carcinoma.
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PMID:Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas. 1507 39

The expression of the trefoil factor family (TFF) genes (TFF1, TFF2, and TFF3) was systematically analyzed in 18 different organs from male or female mice using RT-PCR analysis. The expression patterns showed some gender-specific differences, e.g., TFF3 transcripts in the urinary bladder and liver. Furthermore, the murine expression profile differed from that in human, e.g., in the respiratory tract and uterine cervix. As a hallmark, an aberrant TFF1-related transcript was detected specifically in the kidney and liver of several mouse strains. Molecular characterization of this rare 1.8kb long transcript from the kidney clearly revealed that its 3' region originated from the antisense strand of the TFF1 locus containing particularly large parts of the antisense strands of introns 1 and 2. Homology searches using various databases revealed that this antisense TFF1-related transcript is subject of intense alternative splicing and no protein product encoded by this antisense TFF1-related transcript could be identified. Although the function of this transcript is not known currently, we can speculate that this antisense TFF1-related transcript might have a gene silencing effect particularly on TFF1 expression in the murine kidney and liver.
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PMID:Profiling trefoil factor family (TFF) expression in the mouse: identification of an antisense TFF1-related transcript in the kidney and liver. 1517 69

At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor-alpha (TNF-alpha) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett's esophagus.
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PMID:TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD). 1517 71

We studied the expression of trefoil peptides in the different types of intestinal metaplasia of the stomach. Endoscopic biopsy was performed in 132 patients with dyspepsia. Intestinal metaplasia subtype was classified according to the pattern of alcian blue/PAS staining and high iron diamine staining. Expression of trefoil peptides was measured by immunohistochemistry. TFF1 and TFF3 were mainly expressed in goblet cells and TFF2 in columnar cells in all the types of intestinal metaplasia. There was a gradual decrease of TFF1 and TFF3, and increase of TFF2, during the progression of intestinal metaplasia from type I to type III via the type II intermediate.
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PMID:Expression of trefoil peptides in the subtypes of intestinal metaplasia. 1517 72

TFF peptides (formerly P domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and are thought to influence the rheological properties of mucous gels. We investigated the localization of these peptides in the human false vocal folds of the larynx, also known as the ventricular folds or vestibular folds. An analysis of TFF peptide mRNA by RT-PCR and TFF protein by Western blot detected TFF1 and TFF3, but not TFF2. Immunohistochemistry revealed TFF1 to be associated with the secretory product of goblet cells and mucous parts of subepithelial seromucous glands. TFF3 occurred in columnar epithelial cells of the mucosa and in serous cells and excretory duct cells of seromucous glands. These peptides may play a role in the rheological function of mucus secreted onto the true vocal folds and are thus important constituents of vocal production.
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PMID:TFF peptides in the human false vocal folds of the larynx. 1517 76

Trefoil factor family (TFF) peptides, besides their prominent expression in mucous epithelia, are also synthesized in the central nervous system. Previously TFF1 expression was observed in mouse brain astrocytes, while oxytocinergic neurons of the hypothalamo-pituitary axis are recognized sites of TFF3 synthesis. Here, the expression of TFF1, TFF2, and TFF3 was systematically studied using reverse transcription-polymerase chain reaction (RT-PCR) analysis of dissected adult mouse brain regions including the pituitary. Additionally, the developmental profile of TFF expression in murine cerebral cortex and cerebellum was monitored. Overall, the expression patterns of the three TFF genes differed. The TFF1 and TFF2 profiles shared some similarities, whereas the TFF3 expression pattern was completely different. TFF1 was nearly uniformly, but weakly expressed in all brain regions tested. The TFF1 and TFF2 expression patterns differed characteristically in the pituitary where abundant TFF2 transcription was detected in the anterior and not the posterior lobe and the expression level in males was higher than in females. In contrast, TFF3 expression was limited to the hippocampus, the temporal cortex, and the cerebellum, the latter being surprisingly the major site of expression. Here, TFF3 mRNA appeared to be restricted mainly to neurons and not glial cells. Cerebellar TFF3 expression is clearly developmentally regulated (maximum at P15), indicating a role for TFF3 during postnatal cerebellar development.
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PMID:Trefoil factor family (TFF) expression in the mouse brain and pituitary: changes in the developing cerebellum. 1517 78

Necrotising enterocolitis (NEC) remains an overwhelming gastrointestinal (GI) emergency in premature infants, with an annual incidence of 350 cases and a mortality of 23% in the United Kingdom. The aetiology of NEC is multifactorial and its pathogenesis poorly understood. It is characterised by severe necrotic damage to the intestine. Mucus is an adherent, viscoelastic gel layer protecting the delicate underlying epithelium from lumenal aggressors such as digestive enzymes and bacterial toxins. The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. These secreted peptides have been identified in a site-specific pattern in the GI mucosa, and their expression has been shown to be upregulated in early stages of mucosal repair. The role of trefoil peptides in neonatal mucosal protection has not been well investigated. Impaired mucosal regeneration due in part to failure of upregulation of TFF expression may contribute to the pathogenesis of NEC. The aim of this study was to investigate TFF1-3 mRNA expression and to identify the gene product in the GI tracts of normal neonatal controls and infants with NEC. Parents of all babies having a laparotomy in the neonatal period (defined as up to 44 weeks' gestation) and bowel resection were approached for written consent. Bowel samples were fixed in formalin and then embedded in paraffin in an RNAse-free manner. In situ hybridisation and immunohistochemistry were performed to examine the pattern of trefoil mRNA expression and to localise the peptides in the neonatal GI tract. Forty neonatal bowel specimens were examined. Twelve patients had NEC, eight were recovering from NEC, and 20 control specimens were obtained. TFF1 and TFF2 mRNA expression were not detected in the majority of NEC specimens, and there was a relative downregulation of TFF3 expression in 83% of NEC patients. TFF1 and TFF2 expression were noted in the recovery phase from NEC. Immunohistochemistry revealed a decrease in TFF3 gene product in sites adjacent to mucosal damage secondary to NEC. In acute NEC there was no apparent expression of TFF1 and 2 protein. In the group of patients recovering from NEC, TFF1 and 2 expression were seen in association with regenerative changes in the mucosa. Previous data has shown TFF1-3 to be upregulated in the acute phase response to mucosal injury in the gut. Trefoil peptides have been shown to promote epithelial cell migration and protect against apoptosis. Our results suggest that there is a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.
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PMID:Impaired mucosal regeneration in neonatal necrotising enterocolitis. 1557 91

Vater's ampulla is of great clinical relevance with regard to the influx of chyme, ascending inflammation, intubation during diagnostic and therapeutic endoscopic maneuvers, therapeutic papillotomy and, especially, the formation of malignancies. Little is known about the distribution of trefoil factor family (TFF) peptides in the ampulla. We have therefore examined TFF peptide distribution in the normal ampulla of Vater and compared it with that in duodenal mucosa and Brunner's glands. Expression and synthesis of TFF peptides in Vater's ampulla and duodenum was investigated by reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. The samples studied originated from 30 autopsy cases with short postmortem intervals. TFF3 was expressed in the ampulla of Vater. mRNA expression of TFF1 was detected in only approximately 25% of the investigated samples. Western blot revealed the production of TFF3 and immunohistochemistry showed that TFF3 was the product of goblet cells. TFF peptide composition of Vater's ampulla varied in comparison with that in the duodenum regarding TFF2 expression. The ampulla of Vater thus has a unique profile of TFF peptide production, supporting the hypothesis that the ampulla is an autonomous organ. The observed differences in the TFF peptide distribution between the duodenum and Vater's ampulla favour the investigation of TFF peptides as prognostic markers in the classification of ampullary carcinomas.
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PMID:Trefoil factor family (TFF) peptides of normal human Vater's ampulla. 1590 65

H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice results in the development of an aberrant 'mucus-rich' cell population. 'Mucus-rich' cells have been described in stomachs of mice with autoimmune gastritis, a disease mediated by CD4+ T cells. Other pathological features of autoimmune gastritis are similar to those in H+/K+ beta-deficient mice and include a mononuclear cell infiltrate in the gastric mucosa, non-functional or absent parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit hypertrophy caused by immature cell hyperplasia. The present study investigates further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA. The involvement of gastrin in regulating trefoil mRNA expression was also investigated using gastrin-deficient mice. In contrast to previous findings, gastrin did not positively regulate TFF1 mRNA expression, but there was possible augmentation of TFF2. Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression.
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PMID:Reciprocal changes in trefoil 1 and 2 expression in stomachs of mice with gastric unit hypertrophy and inflammation. 1598 82

We have investigated how gastric H. pylori infection affects antrum secretory cell types by studying the expression of secretory proteins in antrum epithelium. Antrum biopsy specimens were prospectively collected from 102 individuals (49 H. pylori-infected). Immunohistochemistry was performed for secretory mucins (MUC5AC, MUC5B, MUC6), Trefoil factor family (TFF)-peptides (TFF1, TFF2), endocrine peptides (gastrin, chromogranin A), and proliferating cells (Ki-67). Protein expression was quantified morphometrically. H. pylori infection was significantly correlated to mucosal inflammation and to epithelial atrophy and proliferation. In H. pylori-infected patients the number of proliferating cells increased significantly, and the zone of proliferating cells shifted toward the surface epithelium of the antral glands. Infection was correlated with decreased MUC5AC, TFF1, and TFF2 expression and increased MUC6 and MUC5B expression. Endocrine cells expressing chromagranin A and gastrin shifted toward the surface epithelium of the antral glands in H. pylori-infected patients. H. pylori infection and concomitant inflammation induced increased epithelial proliferation and triggered coordinate deregulation of secretory cell populations in the antrum. In particular, infection led to a coordinated increase in cells expressing MUC6 and MUC5B at the expense of MUC5AC-producing cells.
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PMID:Infection with Helicobacter pylori affects all major secretory cell populations in the human antrum. 1598 58


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