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)

Neoplastic transformation of epithelial cells is commonly associated with alterations in the expression of mucin genes. The mechanisms involved in this process are largely unknown. MUC6, isolated from a stomach cDNA library, is mainly expressed in stomach antral glands, as detected by using in situ hybridization and immunohistochemistry. We examined MUC6 expression in normal and pathological breast tissues using immunohistochemistry with MUC6-specific antibodies and in cultured breast cancer cells using immunocytochemistry and Northern blotting. MUC6 was generally not detected in normal breast (1/11) but was detected in fibrocystic disease without atypia (7/17, 41%), in atypical fibrocystic disease (11/11, 100%) and in carcinoma (57/60, 95%). To study the mechanisms involved in mucin gene up-regulation in breast cancer, we examined baseline, growth-related and steroid-induced levels of MUC1, MUC3 and MUC6 in 4 breast cancer cell lines, 2 of which express estrogen receptors. MUC6 levels were up-regulated at post-confluence in 2/4 cell lines, whereas no changes were detected for the other mucin genes examined. MUC6 and MUC3 were constitutively expressed, and steroid-induced, in BT-474 and MCF-7 cells, respectively. As a control, pS2 was induced in both cell lines. Our results indicate that (1) MUC6 is overexpressed in breast cancer and in benign breast disease, (2) in vitro, MUC6 and MUC3 are up-regulated by steroids and (3) abnormal expression of MUC6 in breast cancers may, in part, be explained by hormonal changes associated with tumor development.
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PMID:MUC6 expression in breast tissues and cultured cells: abnormal expression in tumors and regulation by steroid hormones. 965 May 51

The expression of two trefoil peptides (TFF1 and TFF2) and four mucins (MUC1, MUC2, MUC5AC, and MUC6) was evaluated by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 29 gastric polyps, 10 hyperplastic and 19 adenomatous, eight of which displayed malignant transformation. The aims of this study were to characterize the expression profile of these molecules in each type of polyp and to investigate possible modifications of the profile during the process of malignant transformation. All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells. In adenomatous polyps, three main phenotypes could be identified: complete gastric phenotype (co-expression of TFF1 and MUC5AC)-nine cases (47.4 per cent); incomplete gastric phenotype (TFF1-positive and MUC5AC-negative)-seven cases (36.8 per cent); non-gastric (intestinal) phenotype (no expression of TFF1 or MUC5AC)-three cases (15.8 per cent). Data yielded by immunohistochemistry and RT-PCR showed a good correlation for both TFF1 and TFF2. One hyperplastic and seven adenomatous polyps with villous architecture displayed foci of diffuse and intestinal-type carcinoma, respectively; in all of these cases, MUC1 expression and signs of gastric differentiation were observed in both the non-malignant and the carcinomatous component. It is concluded that gastric differentiation is a feature of hyperplastic polyps and of a subset of adenomatous polyps which is shared by early carcinomas arising in some of these polyps, regardless of the histological type of polyp and of carcinoma.
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PMID:Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation. 1039 19

The expression of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6) has previously been described in gastric polyps. In the present study, the expression profile of these trefoil peptides and mucins was characterized in 96 gastric carcinomas, in an attempt to further the understanding of the histogenesis and cell differentiation of gastric carcinoma. Taking together the co-expression of trefoil peptides and mucins, three phenotypes were defined: complete gastric, incomplete gastric, and non-gastric phenotype. Gastric differentiation (complete and incomplete) was observed in 30 out of 33 (90.9%) diffuse carcinomas and in 38 out of 53 (71.7%) intestinal carcinomas. Non-gastric differentiation was observed in only three (9.1%) diffuse carcinomas and in 15 (28.3%) intestinal carcinomas. The phenotypes observed in intestinal carcinomas were similar to those previously observed in adenomatous polyps, whereas most diffuse carcinomas mimicked the phenotype of hyperplastic polyps. The percentage of cases displaying a non-gastric phenotype was higher, though not significantly, in tumours that had invaded the gastric wall than in T1 tumours, regardless of histotype. It is concluded that gastric-type differentiation is retained in the majority of gastric carcinomas, being more prominent in diffuse than in intestinal carcinomas, and in early than in advanced carcinomas.
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PMID:Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). 1069 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

The origin of gastric metaplasia of the duodenum (GMD) remains enigmatic. We studied expression of mucins and trefoil peptides in GMD to gain insight into its phenotype and origin. We examined duodenal tissue of 95 patients (0 to 83 years old, 26 with gastric Helicobacter pylori infection) for the presence of GMD. Expression was examined immunohistochemically of secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), trefoil peptides (TFF1, TFF2, and TFF3), and sucrase-isomaltase (SI). GMD, found in 37 patients, correlated positively to gastric H. pylori infection, age, and villus atrophy. MUC2 and TFF3, expressed in normal goblet cells, were absent from 100% and 87% of GMD, respectively. GMD ubiquitously expressed MUC5AC, whereas MUC5AC expression in adjacent goblet cells was closely correlated with the extent of GMD. TFF1, TFF2, and MUC6 were found in 84%, 92%, and 65% of GMD, respectively. MUC5B was absent from epithelium and GMD. SI, expressed by villus enterocytes, was absent from GMD. Brunner's glands ubiquitously expressed MUC5B, MUC6, and TFF2. GMD was characterized by the expression of gastric-type proteins MUC5AC, MUC6, TFF1, and TFF2 and the absence of intestinal markers MUC2, TFF3, and SI. In terms of the location of metaplastic cells, our results suggest that epithelial cells migrating toward villus tips switch to gastric-type secretory cells. Positive correlation with infection suggests an inductive role H. pylori in the development of GMD.
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PMID:Metaplasia of the duodenum shows a Helicobacter pylori-correlated differentiation into gastric-type protein expression. 1261 84

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 trefoil protein TFF1 is expressed principally in the superficial cells of the gastric mucosa. It is a small protein and forms homo- and hetero-dimers via a disulphide bond through Cys58 which is located three amino acids from the C terminus. TFF1 is co-expressed with the secreted mucin MUC5AC in superficial cells of the gastric mucosa suggesting that it could be involved in the packaging or function of gastric mucus. We have previously shown that TFF1 co-sediments with mucin glycoproteins on caesium chloride gradients. To extend this observation we have now used gel filtration under physiological conditions, immunoprecipitation and Western transfer analysis to characterise the interaction of TFF1 with gastric mucin glycoproteins. We show that TFF1 co-elutes with MUC5AC but not MUC6 on gel filtration and that immunoprecipitation and Western transfer analysis confirms that TFF1 interacts with MUC5AC. We also demonstrate that the TFF1 dimer is the predominant molecular form bound to MUC5AC. Salt and chelators of divalent cations such as EDTA and EGTA disrupted the TFF1- MUC5AC interaction and increased the degradation of MUC5AC, whereas calcium increased the amount of TFF1 bound to MUC5AC. These data support the contention that TFF1 is pivotal in the packaging and function of human gastric mucosa.
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PMID:The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa. 1528 36

Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6, KLF4, and TFF1, was found to be up-regulated in PanIN. Up-regulation of these genes was further validated using combinations of real-time reverse transcription-PCR, in situ hybridization, and immunohistochemistry in a total of 150 early PanIN lesions from 81 patients. Identification of these gastrointestinal transcripts in human PanIN prompted assessment of other foregut markers by both semiquantitative and real-time reverse transcription-PCR, revealing similar up-regulation of Sox-2, Gastrin, HoxA5, GATA4/5/6, Villin and Forkhead 6 (Foxl1). In contrast to frequent expression of multiple gastric epithelial markers, the intestinal markers intestinal fatty acid binding protein, CDX1 and CDX2 were rarely expressed either in PanIN lesions or in invasive pancreatic cancer. Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions. These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.
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PMID:Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. 1575 53

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

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.
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PMID:Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. 1692 27


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