Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episialin, also designated MUC1, CA 15-3 antigen and PEM, is an established serum marker for breast cancer. Its function and possible involvement in tumor progression has not yet been completely established. The molecule is an extended rod-like molecule protruding high above the cell surface. It is often highly overexpressed in breast cancer relative to normal breast epithelium cells. Overexpression of episialin on cells in vitro reduces cell-cell and cell-extracellular matrix adhesion, because the rod-like molecule masks the adhesion receptors. Episialin also exerts its anti-adhesion effect in vivo. In certain human tumors, where episialin was present at the basal side of the cell, abnormal contacts between the plasma membrane and the stroma were observed. As a consequence of its anti-adhesion properties, episialin overexpression reduces the sensitivity of the cells for cytotoxic lymphocytes. This might be one of the reasons why episialin transfected cells are more potent to form experimental metastases after i.v. injection into nude mice.
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PMID:Is episialin/MUC1 involved in breast cancer progression? 772 39

Studies about the function of mucin molecules as surface molecule of adenocarcinoma of gastrointestinal tract had just started, and several important function of mucins had been revealed. In the process of the malignant transformation, class of the expressed mucin core protein and content of glycochain of mucin molecule was changed. Changes of glycoprotein of mucin molecule during transformation affect immunogenesity, tumorigenesity, metastatic ability and sensitivity for anti-cancer drugs. Glycosylated mucin acts important roles during metastatic sequence and prognosis of the gastrointestinal cancer was collerated with expression of immatured mucin of cancer cells. A type of mucin with immature type of glycochain, MUC1, had a protective function for cytotoxicity, e.g. natural killer cell and cytotoxic T-cell, and deglycosilation of MUC1 sensitize cancer cells for cytotoxicity. And MUC1 reduce sensitivity for anti-cancer drugs and MUC1 was glycosilated during process to get resistance for anti-cancer drug. The functions of mucin molecules is not fully revealed, but further studies will indicate importance of mucin molecules in tumor progression.
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PMID:[Functions of mucin molecules in gastrointestinal cancer]. 863 44

MUC1 mucin is found in a variety of epithelial tissues and is overexpressed in several epithelial cancers. This molecule could modulate cellular adhesion and thereby influence tumor invasion and metastasis. Little is known of MUC1 gene expression in thyroid tissues. We investigated whether MUC1 mucin gene alteration and/or expression correlated with thyroid tumor progression by studying 21 fresh thyroid tissue specimens comprising 10 macrofollicular adenomas and 11 papillary carcinomas. Normal adjacent tissue from the same patients was also studied. To determine the integrity and expression of the MUC1 mucin gene, a complementary DNA (cDNA) probe was used for Southern blot analysis of DNA and Northern blot analysis of RNA. A detailed immunohistochemical analysis of MUC1 protein expression was performed with DF3 monoclonal antibody, and was compared with other tumor characteristics and clinical manifestations at diagnosis. Of the 14 tumors informative (heterozygous) with the pMUC10 polymorphic probe, 2 (14%) showed loss of heterozygosity (1 adenoma and 1 carcinoma). Overexpression of MUC1 RNA, compared with normal thyroid tissue, was observed in 6 of the 11 papillary carcinomas and in none of the 10 adenomas. Immunostaining of the corresponding formalin-fixed paraffin-embedded tissue sections detected MUC1 mucin protein at the apical domain of follicular cells. Most of the lining was thin in normal tissue and follicular adenomas, but the protein was more irregularly and less strongly expressed in adenomas. In carcinomas the epithelial mucin produced by the MUC1 gene was present irregularly as a thin and/or thick lining at the apical domain of tumor cells. In addition, 5 of the 6 samples with MUC1 mRNA overexpression showed intracytoplasmic staining. Moreover, intracytoplasmic MUC1 mucin staining was found in 75% of "high-risk" papillary thyroid carcinoma (PTC) (PTC with extrathyroid extension at initial diagnosis and/or lymph node involvement), and in only 28.5% of "low-risk" PTC (purely intrathyroidal carcinomas).
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PMID:MUC1 mucin gene, transcripts, and protein in adenomas and papillary carcinomas of the thyroid. 934 75

On the basis of their known fine specificities we evaluated the immunohistochemical marker qualities of two monoclonal antibodies (mabs) defining the tumor-associated TF disaccharide Gal beta 1-3 GalNAc. This antigen is expressed in certain tumors in correlation with prognosis and metastasis. The reactivity of one of these mabs (A78-G/A7) depends on clustered TF disaccharides (glycosylation at vicinal Ser/Thr positions) while the other--mab BW835--has been characterized to bind specifically to TF disaccharide linked to a motif within the MUC1 repeat. Therefore, mab BW835 represents an interesting tool for the identification of tumor-associated glycoforms of MUC1, which are involved in tumor progression and metastasis, but also in the recognition of tumor cells by cytotoxic T cells. As references the TF-binding lectins from peanut (PNA) and Artocarpus integrifolia (jacalin) were applied. The binding patterns of these immunoreagents were strikingly distinct. Mab BW835 showed a significantly stronger reactivity than mab A78-G/A7, especially in gastric, mammary, pancreatic, thyreoideal, renal and bladder carcinomas. PNA and jacalin receptors exhibited an expression in the majority of all cancer types, with the exception of seminoma and glioblastoma/sarcoma. These results can be explained by the broader fine specificities of the lectins. Furthermore, a strong expression of MUC1-bound TF antigen is indicated by the staining pattern of mab BW835. The marker qualities of both antigens, TF and MUC1, are combined in the binding specificity of BW835, and hence this antibody may have a high impact for the immunodetection of these tumor-associated antigens.
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PMID:Immunoreactivity of Thomsen-Friedenreich (TF) antigen in human neoplasms: the importance of carrier-specific glycotope expression on MUC1. 1050 31

MUC1 mucin is a target protein for many monoclonal antibodies. Human MUC1 detected by a murine anti-KL-6 monoclonal antibody that recognizes a sialylated carbohydrate chain has been designated KL-6/MUC1. Given the heterogeneous antigenicity of KL-6/MUC1, we established a new murine monoclonal antibody, H9, that reacts with epitope DTRP (Asp-Thr-Arg-Pro) peptides within the immunodominant region of the tandem repeat of MUC1 mucin. The reactivity of the H9 antibody differs from that of other previously reported antibodies that recognize the tandem repeat region of MUC1. Immunohistochemical experiments indicate that the reactivity of the H9 antibody is similar to that of other antibodies directed against MUC1 core proteins. A new cancer-associated protein detected by a sandwich assay using the H9 antibody as a catcher and the KL-6 antibody as a tracer is designated HK9. Serum HK9 levels showed a high expression level in lung cancer: 51% (19/37 cases) for adenocarcinoma, 39% (11/28 cases) for squamous cell carcinoma, and 67% (10/15 cases) for small cell carcinoma. The HK9 expression in lung cancer increased with cancer progression. These findings suggest monoclonal antibody H9 to be a novel antibody that reacts with an epitope within the tandem repeat region of MUC1, and that the cancer-associated antigen HK9 may have useful tumor-associated properties.
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PMID:A novel monoclonal antibody, H9, directed against the core protein of MUC1 mucin. 1067 62

The band 1q21 is among the most common sites affected by chromosomal translocations in lymphoid, myeloid, epithelial, and sarcomatous lesions. In non-Hodgkin's lymphoma (NHL), translocations and duplications affecting this chromosomal site are frequently, but not exclusively, seen in association with primary abnormalities such as the t(14;18)(q32;q21) and t(8;14)(q24;q32) translocations, suggesting a role for 1q21 rearrangements in tumor progression. We report here the characterization and cloning of breakpoints in a case of extranodal ascitic B-cell lymphoma with a t(1;14)(q21;q32) translocation. The breakpoints on the der(1) and der(14) chromosomes were mapped by fluorescence in situ hybridization and Southern blot analysis and cloned using an IGHG (Cgamma) probe. The translocation linked the IGHG4 switch (Sgamma4) sequences of the productively rearranged allele to chromosome 1 sequences downstream of MUC1, leaving the MUC1 transcriptional unit intact. MUC1 was markedly overexpressed in the tumor at the mRNA and protein levels relative to lymphoma cell lines lacking a 1q21 rearrangement. Presumably, MUC1 transcription is aberrantly regulated by the IGHA (Calpha) 3' enhancer element retained on the same chromosome. Screening of a panel of B-cell lymphomas by Southern blot analysis identified a subset with a 3' MUC1 breakpoint and another with low-level amplification of MUC1. MUC-1 mucin has previously been shown to be frequently overexpressed in human epithelial cancers and to be associated with tumor progression and poor clinical outcome. Thus, MUC1 activation by chromosomal translocation, rearrangement, and amplification, identified here for the first time in NHL, is consistent with its suggested role in tumorigenesis. (Blood. 2000;95:2666-2671)
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PMID:MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets. 1075 49

Pancreatic cancer is a highly aggressive, treatment refractory cancer and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas overexpress altered forms of a tumor-specific Ag, mucin 1 (MUC1; an epithelial mucin glycoprotein), which is a potential target for immunotherapy. We have established a clinically relevant animal model for pancreatic cancer by developing a double transgenic mouse model (called MET) that expresses human MUC1 as self molecule and develops spontaneous tumors of the pancreas. These mice exhibit acinar cell dysplasia at birth, which progresses to microadenomas and acinar cell carcinomas. The tumors express large amounts of underglycosylated MUC1 similar to humans. Tumor-bearing MET mice develop low affinity MUC1-specific CTLs that have no effect on the spontaneously occurring pancreatic tumors in vivo. However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity. These CTLs were MHC class I restricted and recognized peptide epitopes in the immunodominant tandem repeat region of MUC1. The MET mice appropriately mimic the human condition and are an excellent model with which to elucidate the native immune responses that develop during tumor progression and to develop effective antitumor vaccine strategies.
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PMID:Mice with spontaneous pancreatic cancer naturally develop MUC-1-specific CTLs that eradicate tumors when adoptively transferred. 1097 66

According to studies on a variety of malignant tumors from different organs MUC1 mucin antigen presents as a valuable marker of cancer progression and prognosis. During recent years, a great number of monoclonal antibodies (mabs) directed to MUC1 was generated. Their epitopes can be classified according to their position within the tandem repeat domain of the mucin and with respect to effects exerted by site-specific glycosylation. In this study, eight mabs from different clusters were selected to correlate their epitope specificity with their binding pattern in human cancer specimens. By applying an immunohistochemical ABC-peroxidase method, ten carcinomas derived from breast, pancreas, stomach and colon were characterized. A positive reaction of all mabs could be observed in the majority of the carcinomas, however, the extent of the stained tumor area varied significantly. In general, mabs M38, VA1 and BC3 exhibited the strongest staining reaction. Mab BW835 showed a similar binding intensity, especially in pancreatic and gastric carcinomas. It is tempting to speculate that the different binding patterns may reflect differences in epitope specificity. In conclusion, future immunohistochemical, immunoserological and therapeutic studies involving MUC1 antigen should prefer well-characterized and highly reactive mabs detecting defined peptide epitopes.
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PMID:Epitope-dependent differential immunoreactivities of anti-MUC1 monoclonal antibodies in human carcinomas. 1117 79

Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self-antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce.
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PMID:Human MUC1 mucin: a multifaceted glycoprotein. 1119 32

MUC1 (DF3 antigen) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that MUC1 is expressed in tumors of various human organs and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of MUC1 have not yet been established in human esophageal carcinomas. In this study, we examined MUC1 expression and its histopathological localization in human esophageal squamous cell carcinoma. MUC1 immunoreactivity was found in 17 (32.1%) out of 53 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, vascular invasion or lymph node status. MUC1 expression was detected in the intramucosal part in 28.3% (15 out of 53) and in the invasive part in 32.6% (14 out of 43) of the esophageal carcinomas (no significant difference). These observations suggested that expression of MUC1 is an early event in cancer progression, but that it is not significantly associated with metastasis of human esophageal carcinomas.
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PMID:Immunohistochemical MUC1 (DF3 antigen) expression of human esophageal squamous cell carcinoma. 1139


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