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)

Trefoil factor family (TFF) peptides are typical secretory products of mucin-producing cells, e.g. of the gastrointestinal tract. Here, the expression and secretion of mucins and TFF peptides was studied in the HT-29 cell line throughout cellular growth and differentiation in relation to a mucin-secreting (HT-29 MTX) or an enterocyte-like (HT-29 G(-)) phenotype. mRNAs of several MUC and TFF genes were expressed in both cell subpopulations. However, for most MUC and TFF genes, the expression appeared strongly induced with the differentiation into the mucin-secreting phenotype. On the other hand, TFF2 was specifically expressed in the mucin-secreting HT-29 MTX cells. The differentiation of HT-29 MTX cells into the mucin-secreting phenotype was characterised by secretion of the gel-forming mucins MUC2, MUC5AC, and MUC5B, however, according to a different pattern in the course of differentiation. A significant amount of TFF1 and TFF3 was secreted after differentiation, also according to a different pattern, whereas TFF2 was only faintly detected. Secretagogues, known to induce the secretion of mucus, increased the secretion of all three TFF peptides. In contrast, neither a secretory mucin nor a TFF peptide was found in the culture medium of HT-29 G(-) cells. Overlay assays indicated that HT-29 MTX mucins bound to secretory peptides of HT-29 MTX cells with relative molecular mass similar to TFF peptides. TFF1 and TFF3 were specifically localised in the mucus layer of HT-29 MTX cells by confocal microscopy. Finally, the secretion of TFF peptides and mucins appears as a co-ordinated process which only occurs after differentiation into goblet cell-like phenotype.
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PMID:Specific secretion of gel-forming mucins and TFF peptides in HT-29 cells of mucin-secreting phenotype. 1138 69

The molecular architecture of the human ocular mucus is not yet completely understood. Recently, TFF peptides (formerly known as trefoil factors or P-domain peptides) could be identified as new constituents of this delicate mucus. Members of the TFF-peptide family are typical secretory products of mucous epithelia and three are known in humans and designated as TFF1, TFF2 and TFF3. They enhance cell migratory processes (motogenic effect), they show anti-apoptotic effects and are inflammatory modulators Both TFF1 and TFF3 expression could be monitored by the reverse transcription-polymerase chain reaction (RT-PCR) in the human conjunctiva; in contrast, TFF2 transcripts were not detectable. Using immunohistochemistry, TFF1 and TFF3 peptides were found in varying concentrations solely in secretory vesicles of conjunctival goblet cells. This localisation matches precisely that of the secretory mucin MUC5AC. Thus, conjunctival TFF1 and TFF3 have to be considered as typical mucin-associated peptides probably modulating the rheological properties of the ocular mucus and the tear fluid. Future investigations are in progress to elucidate the role of TFF-peptides during pathological conditions of the eye as well as their diagnostic and therapeutic potential.
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PMID:[TFF peptides. New mucus-associated secretory products of the conjunctiva]. 1169 22

This study examines the coexpression of MUC1 mucin and trefoil factor 1 (TFF1) and their relationship to progression of renal cell carcinoma (RCC). Immunohistochemistry was performed on tumor and adjacent normal tissue from clear-cell RCC (n = 60) and tissues from normal controls (n = 5) using a set of well-characterized monoclonal antibodies recognizing different epitopes of MUC1 and TFF1. Results of immunohistochemistry were compared with clinical parameters, including tumor grade, tumor size, presence of metastasis, and progression-free survival of patients after surgery. In normal tissue, MUC1 and TFF1 were absent from the normal proximal tubular epithelium but were identified in distal and collecting tubular epithelium. In RCC, increased MUC1 expression positively correlated to tumor progression. MUC1 recognized by HMFG1 was associated with large tumor size (P < .05), distant metastasis (P < .05), and invasion of large veins (P < .05). Expression of the under-glycosylated form of MUC1 recognized by SM3 was found to correlate to time to progression (recurrence, metastasis, or death of patient; P < .001). Expression of TFF1 did not significantly correlate with any prognostic parameters. However, there was a significant correlation (P < .01) between TFF1 and MUC1 expression (HMFG2 epitope) in RCCs. These results are consistent with the following conclusions: (1) MUC1 may be an independent prognostic marker in RCC; (2) TFF1 is frequently coexpressed with MUC1 and may act synergistically; and (3) RCC may originate from distal tubular epithelium.
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PMID:MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma: correlation with prognosis. 1182 74

The "TFF domain" is an ancient cysteine-rich shuffled module forming the basic unit for the family of secretory TFF peptides (formerly P-domain peptides and trefoil factors). It is also an integral component of mosaic proteins associated with mucous surfaces. Three mammalian TFF peptides are known (i.e., TFF1-TFF3); however, in Xenopus laevis the pattern is more complex (xP1, xP4.1, xP4.2, and xP2). TFF peptides are typical secretory products of a variety of mucin-producing epithelial cells (e.g., the conjunctiva, the salivary glands, the gastrointestinal tract, the respiratory tract, and the uterus). Each TFF peptide shows an unique expression pattern and different mucin-producing cells are characterized by their specific TFF peptide/secretory mucin combinations. TFF peptides have a pivotal role in maintaining the surface integrity of mucous epithelia in vivo. They are typical constituents of mucus gels, they modulate rapid mucosal repair ("restitution") by their motogenic and their cell scattering activity, they have antiapoptotic effects, and they probably modulate inflammatory processes. Pathological expression of TFF peptides occurs as a result of chronic inflammatory diseases or certain tumors. TFF peptides are also found in the central nervous system, at least in mammals. In particular, TFF3 is synthesized from oxytocinergic neurons of the hypothalamus and is released from the posterior pituitary into the bloodstream.
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PMID:Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain. 1183 92

Barrett's esophagus (BE) consists of metaplastic epithelium of the esophagus, generally diagnosed by mucin histochemistry. We aimed to determine which mucins were expressed in BE, and to relate their expression to BE pathology. Archival biopsies of 4 patient groups were selected, based on standard histochemistry: BE without inflammation, BE with inflammation, ulcerating BE, and BE with dysplasia. Sections were stained by immunohistochemistry for secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), the proliferation marker Ki-67, and mucin-associated trefoil factor family (TFF) peptides (TFF1, TFF2, and TFF3). MUC5AC and TFF2 were expressed at similar high levels in each clinical group. Intestinal metaplasia (IM), detected both histochemically and by the intestinal mucin MUC2, was lowest in inflamed BE. The expression of the intestinal-type TFF3 did not differ among the groups. Ulcerating BE was distinguished by very low expression of MUC6 and MUC5B, but very high expression of TFF1. Proliferation was not different among the groups. In the total group of BE patients, H. pylori infection of the stomach correlated with decreased TFF2 expression in the BE epithelium. We conclude that BE is best characterized by the specific expression of the gastric-type markers, MUC5AC, MUC6, TFF1, and TFF2. Ulcerating BE constitutes the most distinguished group with respect to mucin and TFF expression. Of the intestinal markers, MUC2 is very specific for IM in BE, whereas TFF3 is not a marker for IM. The low occurrence of IM in inflamed BE suggests that these patients may have the lowest risk of developing carcinoma.
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PMID:Barrett's esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2. 1215 67

TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2. Reports of the expression of TFF3 within the normal human stomach are contradictory and the precise localisation of TFF3 is unknown. We have mapped the human gastric mucosa by reverse transcription/polymerase chain reaction and Western blot analysis and by immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus-antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the pyloric region and the proximal duodenum. High TFF1 levels were present in all regions of the gastric mucosa including the corpus, whereas the proximal duodenum was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and pyloric surface mucous cells. In the antrum, an increasing concentration gradient was found towards cells deeper in the isthmus. TFF1 was confined to superficial pit cells in the antrum. TFF3 was also present in specific layers of the laminated mucous gel of the antral and pyloric regions and variable concentrations of TFF3 (2-62 nmol/l) were measured in gastric juice. Here, a probably N-terminally shortened variant is present that forms disulphide-linked dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and pyloric gastric mucosa and has a gastric expression pattern different from that of TFF1 and TFF2. TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa.
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PMID:A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa. 1496 59

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

In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment can lead to columnar-lined esophagus (CLE) including metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). This study describes the morphology and phenotypic features of CLE and EAC in the rat model and compares them with the corresponding lesions in human Barrett's esophagus (BE). Swiss roll preparations of esophagi of EGDA rats and biopsies from human BE containing specialized intestinal metaplasia (SIM) and EAC were examined. The esophagi of EGDA rats showed esophagitis, CLE, islands of multilayered epithelium (MLE), dysplasia and EAC. The CLE had features of specialized intestinal metaplasia. MLE frequently occurred at the neo-squamocolumnar junction and occasionally in the mid-esophagus in isolated foci. Scattered mucinous cells in esophageal squamous epithelium were also found. The CLE and MLE in EGDA rats resembled the lesions described in human BE in morphology, mucin features and expression of differentiation markers (CK7, CK20, Das-1, villin, and pS2/TFF1). Invasive EAC in EGDA rat is of well-differentiated mucinous type, which is in contrast to the variably differentiated glandular type of adenocarcinoma in human BE. p53, c-myc, and cyclooxygenase 2 are expressed in both the rat and human SIM and EAC. These studies indicate that, not withstanding small differences, SIM and EAC induced in EGDA rats are similar to the corresponding lesions in human BE. EGDA rats may serve as a useful model to study the pathogenesis, molecular biology, and chemopreventive interventions of human BE and EAC.
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PMID:Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus. 1509 11

Trefoil factor family (TFF) domain peptides, products of mucin-secreting epithelial cells, are thought to influence mucosal integrity. Molecular studies revealed that mammalian TFFs lack transmembrane domains. Using immunocytochemistry and FACS analysis we demonstrated the association of TFF1 with the cell membrane in MCF-7 (a breast adenocarcinoma cell line), and tested the hypothesis that glycosylphosphatidylinositol (GPI) linkage is the mechanism for this association. Cleavage of GPI anchorage using phospholipase C did not affect TFF1 binding to the cell membrane. Our results demonstrate for the first time that TFF1 is associated with the cell membrane of MCF-7 cells and is not linked via a GPI anchor.
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PMID:TFF1 is membrane-associated in breast carcinoma cell line MCF-7. 1517 68

Trefoil factor family (TFF) 1, 2, and 3 is a mucin-associated protein involved in the maintenance of mucosal barrier and restitution of lining epithelial cells. In this study, the expression of TFF1, 2, and 3 and MUC mucins were examined immunohistochemically in hepatolithiasis and control livers. The expression of TFF1, 2, and 3 were augmented markedly in biliary mucosa in hepatolithiasis in coordinate with gel-forming mucin. TFF3 was detected in hepatic bile samples of hepatolithiasis. Augmented expression and secretion of TFF in biliary mucosa in hepatolithiasis may play a role in lithogenesis together with gel-forming mucin in addition to mucosal defense and repair.
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PMID:Expression of trefoil factor family 1, 2, and 3 peptide is augmented in hepatolithiasis. 1517 70


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