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Gene Review

MUC1  -  mucin 1, cell surface associated

Homo sapiens

Synonyms: ADMCKD, ADMCKD1, Breast carcinoma-associated antigen DF3, CA 15-3, CD227, ...
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Disease relevance of MUC1

  • In concert with these results, we show that MUC1 stimulates ERalpha-mediated transcription and contributes to E2-mediated growth and survival of breast cancer cells [1].
  • The MUC1 protein is aberrantly overexpressed by most human breast carcinomas [1].
  • Increased MUC1 immunoreactivity was observed in most adenocarcinomas of the breast, lung, stomach, pancreas, prostate, and ovary [2].
  • The univariate analysis showed that tumor size, intrahepatic metastasis, lymph node metastasis, MUC4 expression, and MUC1 expression were statistically significant risk factors affecting the outcome of the patients with ICC-MF [3].
  • Epithelial ovarian cancers expressed several mucins including MUC1, 2, 4, and 5AC; MUC3 and 5B were rarely expressed [4].
  • These findings indicate that overexpression of MUC1, as found in human breast cancer cells, is of functional importance to repression of the p53 gene [5].
  • The results suggest that expression of the PAM4-reactive antigen may represent an early event in the development of invasive pancreatic adenocarcinoma, and is unrelated to the VNTR peptide core epitopes of MUC1 [6].
  • Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer have been done in various mouse models but none could properly address the role of MUC1 due to low homology between the mouse and the human molecule [7].
  • We propose that interactions of MUC1 and PDGFRbeta induce signal transduction events that influence the metastatic properties of pancreatic adenocarcinoma [8].

Psychiatry related information on MUC1

  • Data from Bland-Altman differential plots suggest the presence of significant individual differences among individual samples, mainly in the region of high concentrations of MUC1 mucins [9].
  • An appreciation of host defense mechanisms, particularly the antiadherence role of glycosaminoglycan (GAG) in the bladder mucin, reinforces clinical recognition of the bladder as the target organ for bacterial attack associated with urinary tract infection [10].
  • 0. Long-term absence was significantly associated with DMS (OR = 2.1, 95%CI 1.0-4.6), EMA (OR = 5.6, 95%CI 1.0-28.7), sleeping poorly at night (OR= 2.6, 95%CI 1.4-5.0), and high depressive symptoms (OR = 2.0, 95%CI 1.0-3.7) according to the CES-D score of >16, after adjusting for multiple confounding variables [11].
  • Is multi-impulsive bulimia a distinct type of bulimia nervosa: Psychopathology and EMA findings [12].
  • The results of applying the PEM approach to synthesize the effect of self-control training on academic and social behavior showed that the treatment was highly or at least moderately effective [13].

High impact information on MUC1

  • This region includes the gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation [14].
  • We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites [15].
  • Overcoming MUC1 mucin-induced immunosuppression with IL-2 combined with active specific immunotherapy might be an effective immunotherapeutic strategy against human adenocarcinomas [16].
  • This MUC1 mucin-induced suppression of T-cell responses can be reversed by the addition of exogenous IL-2 or anti-CD28 monoclonal antibody [16].
  • A number of adenocarcinomas abundantly express and secrete underglycosylated MUC1 mucin [16].

Chemical compound and disease context of MUC1


Biological context of MUC1


Anatomical context of MUC1


Associations of MUC1 with chemical compounds


Physical interactions of MUC1

  • The results demonstrate that the c-Src SH2 domain binds directly to pYEKV and inhibits the interaction between MUC1 and GSK3 beta [30].
  • Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with beta-catenin [17].
  • The results further demonstrate that MUC1 interacts with ZAP-70 [31].
  • It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation [32].
  • FGF1 also induced binding of MUC1 to the heat shock protein 90 (HSP90) chaperone by a mechanism dependent on phosphorylation of the YEKV motif [33].

Enzymatic interactions of MUC1


Regulatory relationships of MUC1

  • CC extensively expressed MUC1 apomucin and focally expressed MUC2 apomucin [36].
  • MUC1 oncoprotein stabilizes and activates estrogen receptor alpha [1].
  • These effects were enhanced by MB2, an antibody against E-cadherin and blocked by monoclonal antibodies (MAbs) 214D4 or M8 against episialin [37].
  • Surprisingly, suppression of MUC1 also inhibited expression of EGFR at both the mRNA and protein levels whereas the reciprocal effect was not observed [38].
  • The results show that IL-7 up-regulates MUC1 on CD4+, CD8+, CD25+, CD69+, naive CD45RA+, and memory CD45RO+ T cells [39].

Other interactions of MUC1

  • These antibodies reacted with the MUC2-derived peptide but not with MUC1- or MUC3-derived peptides [40].
  • The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells [41].
  • Data showed that gp230 was distinct from MUC1 or CD44 [42].
  • A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene [43].
  • All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells [44].
  • MUC1-mediated activation of IKKbeta is dependent on TAK1 and TAB2 [45].
  • Collectively, these data indicate that PIASy may be a useful target for down-regulation of MUC1 expression in various contexts [46].

Analytical, diagnostic and therapeutic context of MUC1


  1. MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Wei, X., Xu, H., Kufe, D. Mol. Cell (2006) [Pubmed]
  2. Heterogeneity of mucin gene expression in normal and neoplastic tissues. Ho, S.B., Niehans, G.A., Lyftogt, C., Yan, P.S., Cherwitz, D.L., Gum, E.T., Dahiya, R., Kim, Y.S. Cancer Res. (1993) [Pubmed]
  3. MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type. Shibahara, H., Tamada, S., Higashi, M., Goto, M., Batra, S.K., Hollingsworth, M.A., Imai, K., Yonezawa, S. Hepatology (2004) [Pubmed]
  4. Mucin gene expression in ovarian cancers. Giuntoli, R.L., Rodriguez, G.C., Whitaker, R.S., Dodge, R., Voynow, J.A. Cancer Res. (1998) [Pubmed]
  5. Human mucin 1 oncoprotein represses transcription of the p53 tumor suppressor gene. Wei, X., Xu, H., Kufe, D. Cancer Res. (2007) [Pubmed]
  6. PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma. Gold, D.V., Karanjawala, Z., Modrak, D.E., Goldenberg, D.M., Hruban, R.H. Clin. Cancer Res. (2007) [Pubmed]
  7. Cutting edge: transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer. Beatty, P.L., Plevy, S.E., Sepulveda, A.R., Finn, O.J. J. Immunol. (2007) [Pubmed]
  8. Platelet-derived growth factor receptor beta-mediated phosphorylation of MUC1 enhances invasiveness in pancreatic adenocarcinoma cells. Singh, P.K., Wen, Y., Swanson, B.J., Shanmugam, K., Kazlauskas, A., Cerny, R.L., Gendler, S.J., Hollingsworth, M.A. Cancer Res. (2007) [Pubmed]
  9. Comparability of eight immunoassay procedures for the determination of CA 15-3 and related markers. Stern, P., Bartos, V., Vavrova, J., Bezdickova, D., Pechova, M., Uhrova, J., Friedecky, B., Sprongl, L., Zima, T., Palicka, V. Clin. Chem. Lab. Med. (2003) [Pubmed]
  10. Overview. New standards for UTI--1988. Parsons, C.L. Urology (1988) [Pubmed]
  11. Association of sickness absence with poor sleep and depressive symptoms in shift workers. Nakata, A., Haratani, T., Takahashi, M., Kawakami, N., Arito, H., Kobayashi, F., Fujioka, Y., Fukui, S., Araki, S. Chronobiol. Int. (2004) [Pubmed]
  12. Is multi-impulsive bulimia a distinct type of bulimia nervosa: Psychopathology and EMA findings. Myers, T.C., Wonderlich, S.A., Crosby, R., Mitchell, J.E., Steffen, K.J., Smyth, J., Miltenberger, R. The International journal of eating disorders. (2006) [Pubmed]
  13. An alternative method for quantitative synthesis of single-subject researches: percentage of data points exceeding the median. Ma, H.H. Behavior modification. (2006) [Pubmed]
  14. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Topaz, O., Shurman, D.L., Bergman, R., Indelman, M., Ratajczak, P., Mizrachi, M., Khamaysi, Z., Behar, D., Petronius, D., Friedman, V., Zelikovic, I., Raimer, S., Metzker, A., Richard, G., Sprecher, E. Nat. Genet. (2004) [Pubmed]
  15. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Kugler, A., Stuhler, G., Walden, P., Zöller, G., Zobywalski, A., Brossart, P., Trefzer, U., Ullrich, S., Müller, C.A., Becker, V., Gross, A.J., Hemmerlein, B., Kanz, L., Müller, G.A., Ringert, R.H. Nat. Med. (2000) [Pubmed]
  16. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2. Agrawal, B., Krantz, M.J., Reddish, M.A., Longenecker, B.M. Nat. Med. (1998) [Pubmed]
  17. Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin. Li, Y., Bharti, A., Chen, D., Gong, J., Kufe, D. Mol. Cell. Biol. (1998) [Pubmed]
  18. Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis. González-Guerrico, A.M., Cafferata, E.G., Radrizzani, M., Marcucci, F., Gruenert, D., Pivetta, O.H., Favaloro, R.R., Laguens, R., Perrone, S.V., Gallo, G.C., Santa-Coloma, T.A. J. Biol. Chem. (2002) [Pubmed]
  19. Low O-acetylation of sialyl-Le(x) contributes to its overexpression in colon carcinoma metastases. Mann, B., Klussmann, E., Vandamme-Feldhaus, V., Iwersen, M., Hanski, M.L., Riecken, E.O., Buhr, H.J., Schauer, R., Kim, Y.S., Hanski, C. Int. J. Cancer (1997) [Pubmed]
  20. Expression of MUC1, MUC2 and oligosaccharide epitopes in breast cancer: prognostic significance of a sialylated MUC1 epitope. Baldus, S.E., Wienand, J.R., Werner, J.P., Landsberg, S., Drebber, U., Hanisch, F.G., Dienes, H.P. Int. J. Oncol. (2005) [Pubmed]
  21. Carbohydrate epitopes and mucins expressed by 17 human ovarian carcinoma cell lines. Tamada, Y., Iida, S., Aoki, D., Nozawa, S., Irimura, T. Oncol. Res. (1999) [Pubmed]
  22. Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells. Gimmi, C.D., Morrison, B.W., Mainprice, B.A., Gribben, J.G., Boussiotis, V.A., Freeman, G.J., Park, S.Y., Watanabe, M., Gong, J., Hayes, D.F., Kufe, D.W., Nadler, L.M. Nat. Med. (1996) [Pubmed]
  23. Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. Wesseling, J., van der Valk, S.W., Vos, H.L., Sonnenberg, A., Hilkens, J. J. Cell Biol. (1995) [Pubmed]
  24. Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma. Retz, M., Lehmann, J., Röder, C., Plötz, B., Harder, J., Eggers, J., Pauluschke, J., Kalthoff, H., Stöckle, M. Cancer Res. (1998) [Pubmed]
  25. The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein. Baruch, A., Hartmann, M., Yoeli, M., Adereth, Y., Greenstein, S., Stadler, Y., Skornik, Y., Zaretsky, J., Smorodinsky, N.I., Keydar, I., Wreschner, D.H. Cancer Res. (1999) [Pubmed]
  26. Evidence that gallbladder epithelial mucin enhances cholesterol cholelithogenesis in MUC1 transgenic mice. Wang, H.H., Afdhal, N.H., Gendler, S.J., Wang, D.Q. Gastroenterology (2006) [Pubmed]
  27. In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Balagué, C., Audié, J.P., Porchet, N., Real, F.X. Gastroenterology (1995) [Pubmed]
  28. The breast mucin MUCI as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer. Regimbald, L.H., Pilarski, L.M., Longenecker, B.M., Reddish, M.A., Zimmermann, G., Hugh, J.C. Cancer Res. (1996) [Pubmed]
  29. Recombinant tumor-associated MUC1 glycoprotein impairs the differentiation and function of dendritic cells. Rughetti, A., Pellicciotta, I., Biffoni, M., Bäckström, M., Link, T., Bennet, E.P., Clausen, H., Noll, T., Hansson, G.C., Burchell, J.M., Frati, L., Taylor-Papadimitriou, J., Nuti, M. J. Immunol. (2005) [Pubmed]
  30. The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin. Li, Y., Kuwahara, H., Ren, J., Wen, G., Kufe, D. J. Biol. Chem. (2001) [Pubmed]
  31. Interaction of human MUC1 and beta-catenin is regulated by Lck and ZAP-70 in activated Jurkat T cells. Li, Q., Ren, J., Kufe, D. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  32. Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function. Baruch, A., Hartmann, M., Zrihan-Licht, S., Greenstein, S., Burstein, M., Keydar, I., Weiss, M., Smorodinsky, N., Wreschner, D.H. Int. J. Cancer (1997) [Pubmed]
  33. MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling. Ren, J., Raina, D., Chen, W., Li, G., Huang, L., Kufe, D. Mol. Cancer Res. (2006) [Pubmed]
  34. O-Linked glycans control glycoprotein processing by antigen-presenting cells: a biochemical approach to the molecular aspects of MUC1 processing by dendritic cells. Hanisch, F.G., Schwientek, T., Von Bergwelt-Baildon, M.S., Schultze, J.L., Finn, O. Eur. J. Immunol. (2003) [Pubmed]
  35. Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder. Miyahara, N., Shoda, J., Kawamoto, T., Furukawa, M., Ueda, T., Todoroki, T., Tanaka, N., Matsuo, K., Yamada, Y., Kohno, K., Irimura, T. Clin. Cancer Res. (2004) [Pubmed]
  36. Characterization of apomucin expression in intrahepatic cholangiocarcinomas and their precursor lesions: an immunohistochemical study. Sasaki, M., Nakanuma, Y., Kim, Y.S. Hepatology (1996) [Pubmed]
  37. Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cells in vitro. Steelant, W.F., Goeman, J.L., Philippé, J., Oomen, L.C., Hilkens, J., Krzewinski-Recchi, M.A., Huet, G., Van der Eycken, J., Delannoy, P., Bruyneel, E.A., Mareel, M.M. Int. J. Cancer (2001) [Pubmed]
  38. Suppression of MUC1 synthesis downregulates expression of the epidermal growth factor receptor. Li, X., Wang, L., Nunes, D.P., Troxler, R.F., Offner, G.D. Cancer Biol. Ther. (2005) [Pubmed]
  39. Dendritic cells induce MUC1 expression and polarization on human T cells by an IL-7-dependent mechanism. Vasir, B., Avigan, D., Wu, Z., Crawford, K., Turnquist, S., Ren, J., Kufe, D. J. Immunol. (2005) [Pubmed]
  40. Second-generation monoclonal antibodies to intestinal MUC2 peptide reactive with colon cancer. Xing, P.X., Prenzoska, J., Layton, G.T., Devine, P.L., McKenzie, I.F. J. Natl. Cancer Inst. (1992) [Pubmed]
  41. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Reis, C.A., David, L., Correa, P., Carneiro, F., de Bolós, C., Garcia, E., Mandel, U., Clausen, H., Sobrinho-Simões, M. Cancer Res. (1999) [Pubmed]
  42. Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas. Nielsen, P.A., Mandel, U., Therkildsen, M.H., Ravn, V., David, L., Reis, C.A., Wandall, H.H., Dabelsteen, E., Clausen, H. Cancer Res. (1997) [Pubmed]
  43. A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene. Hollingsworth, M.A., Closken, C., Harris, A., McDonald, C.D., Pahwa, G.S., Maher, L.J. Nucleic Acids Res. (1994) [Pubmed]
  44. Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation. Nogueira, A.M., Machado, J.C., Carneiro, F., Reis, C.A., Gött, P., Sobrinho-Simões, M. J. Pathol. (1999) [Pubmed]
  45. MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signalling. Ahmad, R., Raina, D., Trivedi, V., Ren, J., Rajabi, H., Kharbanda, S., Kufe, D. Nat. Cell Biol. (2007) [Pubmed]
  46. MUC1 expression is repressed by protein inhibitor of activated signal transducer and activator of transcription-y. Brayman, M.J., Dharmaraj, N., Lagow, E., Carson, D.D. Mol. Endocrinol. (2007) [Pubmed]
  47. A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. Levitin, F., Baruch, A., Weiss, M., Stiegman, K., Hartmann, M.L., Yoeli-Lerner, M., Ziv, R., Zrihan-Licht, S., Shina, S., Gat, A., Lifschitz, B., Simha, M., Stadler, Y., Cholostoy, A., Gil, B., Greaves, D., Keydar, I., Zaretsky, J., Smorodinsky, N., Wreschner, D.H. J. Biol. Chem. (2005) [Pubmed]
  48. The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and Is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer. Sewell, R., Bäckström, M., Dalziel, M., Gschmeissner, S., Karlsson, H., Noll, T., Gätgens, J., Clausen, H., Hansson, G.C., Burchell, J., Taylor-Papadimitriou, J. J. Biol. Chem. (2006) [Pubmed]
  49. Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism. Spicer, A.P., Parry, G., Patton, S., Gendler, S.J. J. Biol. Chem. (1991) [Pubmed]
  50. Mice with spontaneous pancreatic cancer naturally develop MUC-1-specific CTLs that eradicate tumors when adoptively transferred. Mukherjee, P., Ginardi, A.R., Madsen, C.S., Sterner, C.J., Adriance, M.C., Tevethia, M.J., Gendler, S.J. J. Immunol. (2000) [Pubmed]
  51. Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding. Thathiah, A., Blobel, C.P., Carson, D.D. J. Biol. Chem. (2003) [Pubmed]
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