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Gene Review

MUC2  -  mucin 2, oligomeric mucus/gel-forming

Homo sapiens

Synonyms: Intestinal mucin-2, MLP, MUC-2, Mucin-2, SMUC
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Disease relevance of MUC2

  • In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metaplasia [1].
  • In addition, with the exception of prostate cancer, focal aberrant expression of MUC2 and MUC3 epitopes was frequently observed [2].
  • No difference in MUC2 and MUC5AC protein was found between mucinous and non-mucinous carcinomas [3].
  • Low levels of MUC2 mRNA were detected in non-mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive [3].
  • Goblet cells expressing the MUC2 gene and columnar cells expressing the MUC3 gene were consistent with an intestinal phenotype, which was observed in 15 tumours (71%) including nine adenomas and six borderline tumours [4].

High impact information on MUC2

  • These antibodies reacted with the MUC2-derived peptide but not with MUC1- or MUC3-derived peptides [5].
  • Second-generation monoclonal antibodies to intestinal MUC2 peptide reactive with colon cancer [5].
  • RESULTS: In the 22 RVAs, we found an overexpression of MUC2 and an aberrant expression of MUC5AC [6].
  • In pancreas cancer tissues and cell lines, increased expression of MUC2, MUC4, and MUC5C is shown [7].
  • RESULTS: MUC1 is the major apomucin expressed in normal pancreas, whereas MUC2-MUC5 are weakly expressed or undetectable [7].

Chemical compound and disease context of MUC2


Biological context of MUC2

  • In contrast, MUC2 and MUC3 gene expression was primarily restricted to the intestinal tract [2].
  • In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed [13].
  • Rabbit antiserum against a synthetic peptide corresponding to a tandemly repeated amino acid sequence in the human intestinal mucin apoprotein MUC2 was used in immunoprecipitation to study the biosynthesis of MUC2 in the colon-carcinoma cell line LS 174T [14].
  • The 5'-region reveals high degree of sequence similarity with MUC2 and MUC5B and codes for 1336 amino acids organized into a signal peptide, four pro-von Willebrand factor-like D domains (D1, D2, D' and D3) and a short domain which connects to the central repetitive region [15].
  • In patients with clam enterocystoplasty there was evidence of increasing up-regulation of MUC2, 3, 4 and 5AC expression in the urothelium toward the anastomotic site [16].

Anatomical context of MUC2


Associations of MUC2 with chemical compounds


Regulatory relationships of MUC2

  • MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas [24].
  • In contrast, MUC2 mRNA was expressed at only low levels and MUC3 was not detected in the pancreatic tumor cell lines [25].
  • However, the existence of this inhibitory JNK pathways suggests a mechanism whereby--in the absence of NF-kappaB activation--TNF-alpha production during inflammation in vivo could actually inhibit MUC2 production, giving rise to the defective mucosal protection which characterizes inflammatory bowel disease [26].
  • These results suggest that p53 directly activates the MUC2 gene in many cell types [11].
  • Expression of DCC did not modulate constitutive or induced expression of MUC2, nor did DCC induce a mature goblet cell phenotype [27].

Other interactions of MUC2

  • Addition of bile during either storage in UW solution or rewarming period induced increased steady-state MUC2, MUC3 and MUC5AC mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)[28]
  • MUC2 and TFF3 were colocalised throughout the large and small bowel mucosa [29].
  • Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells [30].
  • The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively) [31].
  • Neither cell type showed detectable expression of intestinal MUC2 or gastric MUC6 [32].

Analytical, diagnostic and therapeutic context of MUC2


  1. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Ho, S.B., Shekels, L.L., Toribara, N.W., Kim, Y.S., Lyftogt, C., Cherwitz, D.L., Niehans, G.A. Cancer Res. (1995) [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. Differential expression of the chromosome 11 mucin genes in colorectal cancer. Sylvester, P.A., Myerscough, N., Warren, B.F., Carlstedt, I., Corfield, A.P., Durdey, P., Thomas, M.G. J. Pathol. (2001) [Pubmed]
  4. Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study. Boman, F., Buisine, M.P., Wacrenier, A., Querleu, D., Aubert, J.P., Porchet, N. J. Pathol. (2001) [Pubmed]
  5. 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]
  6. Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma. Buisine, M.P., Janin, A., Maunoury, V., Audié, J.P., Delescaut, M.P., Copin, M.C., Colombel, J.F., Degand, P., Aubert, J.P., Porchet, N. Gastroenterology (1996) [Pubmed]
  7. Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines. Balagué, C., Gambús, G., Carrato, C., Porchet, N., Aubert, J.P., Kim, Y.S., Real, F.X. Gastroenterology (1994) [Pubmed]
  8. MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. Lee, H.S., Lee, H.K., Kim, H.S., Yang, H.K., Kim, Y.I., Kim, W.H. Cancer (2001) [Pubmed]
  9. Partial D-amino acid substitution: Improved enzymatic stability and preserved Ab recognition of a MUC2 epitope peptide. Tugyi, R., Uray, K., Iván, D., Fellinger, E., Perkins, A., Hudecz, F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. O'Connell, J.T., Tomlinson, J.S., Roberts, A.A., McGonigle, K.F., Barsky, S.H. Am. J. Pathol. (2002) [Pubmed]
  11. Transcriptional activation of the MUC2 gene by p53. Ookawa, K., Kudo, T., Aizawa, S., Saito, H., Tsuchida, S. J. Biol. Chem. (2002) [Pubmed]
  12. 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]
  13. Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium. López-Ferrer, A., de Bolós, C., Barranco, C., Garrido, M., Isern, J., Carlstedt, I., Reis, C.A., Torrado, J., Real, F.X. Gut (2000) [Pubmed]
  14. The human MUC2 mucin apoprotein appears to dimerize before O-glycosylation and shares epitopes with the 'insoluble' mucin of rat small intestine. Asker, N., Baeckström, D., Axelsson, M.A., Carlstedt, I., Hansson, G.C. Biochem. J. (1995) [Pubmed]
  15. Human mucin gene MUC5AC: organization of its 5'-region and central repetitive region. Escande, F., Aubert, J.P., Porchet, N., Buisine, M.P. Biochem. J. (2001) [Pubmed]
  16. Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract. N'Dow, J., Pearson, J.P., Bennett, M.K., Neal, D.E., Robson, C.N. J. Urol. (2000) [Pubmed]
  17. 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]
  18. Expression of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from that in normal liver and extrahepatic biliary obstruction. Sasaki, M., Nakanuma, Y., Kim, Y.S. Hepatology (1998) [Pubmed]
  19. Genomic organization of the 3' region of the human mucin gene MUC5B. Desseyn, J.L., Aubert, J.P., Van Seuningen, I., Porchet, N., Laine, A. J. Biol. Chem. (1997) [Pubmed]
  20. Evolutionary history of the 11p15 human mucin gene family. Desseyn, J.L., Buisine, M.P., Porchet, N., Aubert, J.P., Degand, P., Laine, A. J. Mol. Evol. (1998) [Pubmed]
  21. Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1. Hokari, R., Lee, H., Crawley, S.C., Yang, S.C., Gum, J.R., Miura, S., Kim, Y.S. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  22. Expression of human TFF3 in relation to growth of HT-29 cell subpopulations: involvement of PI3-K but not STAT6. Durual, S., Blanchard, C., Estienne, M., Jacquier, M.F., Cuber, J.C., Perrot, V., Laboisse, C., Cuber, J.C. Differentiation (2005) [Pubmed]
  23. Phorbol 12-myristate 13-acetate up-regulates the transcription of MUC2 intestinal mucin via Ras, ERK, and NF-kappa B. Lee, H.W., Ahn, D.H., Crawley, S.C., Li, J.D., Gum, J.R., Basbaum, C.B., Fan, N.Q., Szymkowski, D.E., Han, S.Y., Lee, B.H., Sleisenger, M.H., Kim, Y.S. J. Biol. Chem. (2002) [Pubmed]
  24. Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas. Jang, K.T., Chae, S.W., Sohn, J.H., Park, H.R., Shin, H.S. J. Korean Med. Sci. (2002) [Pubmed]
  25. Expression of MUC1, MUC2, MUC3 and MUC4 mucin mRNAs in human pancreatic and intestinal tumor cell lines. Hollingsworth, M.A., Strawhecker, J.M., Caffrey, T.C., Mack, D.R. Int. J. Cancer (1994) [Pubmed]
  26. TNF-alpha activates MUC2 transcription via NF-kappaB but inhibits via JNK activation. Ahn, D.H., Crawley, S.C., Hokari, R., Kato, S., Yang, S.C., Li, J.D., Kim, Y.S. Cell. Physiol. Biochem. (2005) [Pubmed]
  27. Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene. Velcich, A., Corner, G., Palumbo, L., Augenlicht, L. Oncogene (1999) [Pubmed]
  28. UW-preservation of cultured human gallbladder epithelial cells: phenotypic alterations and differential mucin gene expression in the presence of bile. Campion, J.P., Porchet, N., Aubert, J.P., L'Helgoualc'h, A., Clément, B. Hepatology (1995) [Pubmed]
  29. Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa. Longman, R.J., Douthwaite, J., Sylvester, P.A., Poulsom, R., Corfield, A.P., Thomas, M.G., Wright, N.A. Gut (2000) [Pubmed]
  30. Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Kim, Y.D., Kwon, E.J., Park, D.W., Song, S.Y., Yoon, S.K., Baek, S.H. Mol. Pharmacol. (2002) [Pubmed]
  31. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Chu, P.G., Schwarz, R.E., Lau, S.K., Yen, Y., Weiss, L.M. Am. J. Surg. Pathol. (2005) [Pubmed]
  32. Bile acid-induced alterations of mucin production in differentiated human colon cancer cell lines. Shekels, L.L., Lyftogt, C.T., Ho, S.B. Int. J. Biochem. Cell Biol. (1996) [Pubmed]
  33. Characterization of mucins in human lacrimal sac and nasolacrimal duct. Paulsen, F.P., Corfield, A.P., Hinz, M., Hoffmann, W., Schaudig, U., Thale, A.B., Berry, M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  34. Mucin mRNA expression in lung adenocarcinoma cell lines and tissues. Yu, C.J., Yang, P.C., Shew, J.Y., Hong, T.M., Yang, S.C., Lee, Y.C., Lee, L.N., Luh, K.T., Wu, C.W. Oncology (1996) [Pubmed]
  35. Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Rossi, G., Murer, B., Cavazza, A., Losi, L., Natali, P., Marchioni, A., Migaldi, M., Capitanio, G., Brambilla, E. Am. J. Surg. Pathol. (2004) [Pubmed]
  36. Mucinous differentiation features associated with hormonal escape in a human prostate cancer xenograft. Legrier, M.E., de Pinieux, G., Boyé, K., Arvelo, F., Judde, J.G., Fontaine, J.J., Bara, J., Poupon, M.F. Br. J. Cancer (2004) [Pubmed]
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