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Gene Review

MUC4  -  mucin 4, cell surface associated

Homo sapiens

Synonyms: ASGP, Ascites sialoglycoprotein, HSA276359, MUC-4, Mucin-4, ...
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Disease relevance of MUC4


High impact information on MUC4


Chemical compound and disease context of MUC4


Biological context of MUC4


Anatomical context of MUC4

  • During this developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are located in basal and goblet cells [20].
  • Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism [2].
  • Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland [2].
  • Both MUC1 and MUC4 were up-regulated in transposed ileal segments, genes expressed by the normal human urothelium [21].
  • CONCLUSION: Transposition of ileal segments into the urinary tract results in up-regulation of MUC1 and MUC4, the predominant MUC genes expressed in the human bladder [21].

Associations of MUC4 with chemical compounds

  • Northern blot analysis showed a similar increase for MUC4 and demonstrated that induction of MUC4 and MUC5B expression depended on retinoic acid [22].
  • Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling [2].
  • As a luminal surface component, the MUC4 is situated to contribute to the non-adhesive luminal surface and to act as an intrinsic protection and survival factor [23].
  • To determine whether RA-associated MUC4 mRNA induction is a direct or indirect effect, HCjE cells were treated with RA and the protein synthesis inhibitor cycloheximide (1.0 microg/mL) for 12 hours [24].
  • When correlated with plasma steroid levels, message levels of both MUC4 and MUC5B were inversely related to progesterone levels [25].

Regulatory relationships of MUC4

  • Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-beta, which are relieved during pregnancy to permit secretion of MUC4 into milk [2].
  • Pan-JAK inhibitor revealed marked reduction in IL-4 stimulated MUC4 levels and JAK3 selective inhibitor down-regulated MUC4 mRNA expression in a concentration-dependent fashion [26].

Other interactions of MUC4


Analytical, diagnostic and therapeutic context of MUC4


  1. Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. Terris, B., Dubois, S., Buisine, M.P., Sauvanet, A., Ruszniewski, P., Aubert, J.P., Porchet, N., Couvelard, A., Degott, C., Fléjou, J.F. J. Pathol. (2002) [Pubmed]
  2. Muc4/sialomucin complex in the mammary gland and breast cancer. Carraway, K.L., Price-Schiavi, S.A., Komatsu, M., Jepson, S., Perez, A., Carraway, C.A. Journal of mammary gland biology and neoplasia. (2001) [Pubmed]
  3. Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands. Alos, L., Lujan, B., Castillo, M., Nadal, A., Carreras, M., Caballero, M., de Bolos, C., Cardesa, A. Am. J. Surg. Pathol. (2005) [Pubmed]
  4. Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas. Buisine, M.P., Devisme, L., Degand, P., Dieu, M.C., Gosselin, B., Copin, M.C., Aubert, J.P., Porchet, N. J. Histochem. Cytochem. (2000) [Pubmed]
  5. Normal respiratory mucosa, precursor lesions and lung carcinomas: differential expression of human mucin genes. Copin, M.C., Buisine, M.P., Devisme, L., Leroy, X., Escande, F., Gosselin, B., Aubert, J.P., Porchet, N. Front. Biosci. (2001) [Pubmed]
  6. AMOP, a protein module alternatively spliced in cancer cells. Ciccarelli, F.D., Doerks, T., Bork, P. Trends Biochem. Sci. (2002) [Pubmed]
  7. 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]
  8. 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]
  9. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Nagy, P., Friedländer, E., Tanner, M., Kapanen, A.I., Carraway, K.L., Isola, J., Jovin, T.M. Cancer Res. (2005) [Pubmed]
  10. Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Singh, A.P., Chaturvedi, P., Batra, S.K. Cancer Res. (2007) [Pubmed]
  11. MUC4 is a novel prognostic factor of extrahepatic bile duct carcinoma. Tamada, S., Shibahara, H., Higashi, M., Goto, M., Batra, S.K., Imai, K., Yonezawa, S. Clin. Cancer Res. (2006) [Pubmed]
  12. MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract. Weed, D.T., Gomez-Fernandez, C., Bonfante, E., Lee, T.D., Pacheco, J., Carvajal, M.E., Goodwin, W.J., Carraway, K.L. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. (2001) [Pubmed]
  13. Multidrug resistance correlates with overexpression of Muc4 but inversely with P-glycoprotein and multidrug resistance related protein in transfected human melanoma cells. Hu, Y.P., Haq, B., Carraway, K.L., Savaraj, N., Lampidis, T.J. Biochem. Pharmacol. (2003) [Pubmed]
  14. The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. Funes, M., Miller, J.K., Lai, C., Carraway, K.L., Sweeney, C. J. Biol. Chem. (2006) [Pubmed]
  15. Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study. Arul, G.S., Moorghen, M., Myerscough, N., Alderson, D.A., Spicer, R.D., Corfield, A.P. Gut (2000) [Pubmed]
  16. Developmental expression of mucin genes in the human gastrointestinal system. Reid, C.J., Harris, A. Gut (1998) [Pubmed]
  17. 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]
  18. Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus. Guillem, P., Billeret, V., Buisine, M.P., Flejou, J.F., Lecomte-Houcke, M., Degand, P., Aubert, J.P., Triboulet, J.P., Porchet, N. Int. J. Cancer (2000) [Pubmed]
  19. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. Longman, R.J., Poulsom, R., Corfield, A.P., Warren, B.F., Wright, N.A., Thomas, M.G. J. Histochem. Cytochem. (2006) [Pubmed]
  20. Developmental mucin gene expression in the human respiratory tract. Buisine, M.P., Devisme, L., Copin, M.C., Durand-Réville, M., Gosselin, B., Aubert, J.P., Porchet, N. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  21. 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]
  22. Mucin gene expression during differentiation of human airway epithelia in vitro. Muc4 and muc5b are strongly induced. Bernacki, S.H., Nelson, A.L., Abdullah, L., Sheehan, J.K., Harris, A., Davis, C.W., Randell, S.H. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  23. Presence of MUC4 in human milk and at the luminal surfaces of blood vessels. Zhang, J., Perez, A., Yasin, M., Soto, P., Rong, M., Theodoropoulos, G., Carothers Carraway, C.A., Carraway, K.L. J. Cell. Physiol. (2005) [Pubmed]
  24. Differential regulation of membrane-associated mucins in the human ocular surface epithelium. Hori, Y., Spurr-Michaud, S., Russo, C.L., Argüeso, P., Gipson, I.K. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  25. MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix. Gipson, I.K., Spurr-Michaud, S., Moccia, R., Zhan, Q., Toribara, N., Ho, S.B., Gargiulo, A.R., Hill, J.A. Biol. Reprod. (1999) [Pubmed]
  26. IL-4 induced MUC4 enhancement in respiratory epithelial cells in vitro is mediated through JAK-3 selective signaling. Damera, G., Xia, B., Sachdev, G.P. Respir. Res. (2006) [Pubmed]
  27. Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis. Biemer-Hüttmann, A.E., Walsh, M.D., McGuckin, M.A., Simms, L.A., Young, J., Leggett, B.A., Jass, J.R. Clin. Cancer Res. (2000) [Pubmed]
  28. MUC7 gene expression and genetic polymorphism. Biesbrock, A.R., Bobek, L.A., Levine, M.J. Glycoconj. J. (1997) [Pubmed]
  29. Transcription factor GATA-5 selectively up-regulates mucin gene expression. Ren, C.Y., Akiyama, Y., Miyake, S., Yuasa, Y. J. Cancer Res. Clin. Oncol. (2004) [Pubmed]
  30. Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 AND MUC16. Duraisamy, S., Ramasamy, S., Kharbanda, S., Kufe, D. Gene (2006) [Pubmed]
  31. Expression of gastric mucin in the stomachs of two patients with Menetrier's disease: an immunohistochemical study. Mall, A.S., Taylor, K., Barnard, R., Dent, D.M., Kahn, D. J. Gastroenterol. Hepatol. (2003) [Pubmed]
  32. Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: implications for Muc4/SMC function. Rong, M., Rossi, E.A., Zhang, J., McNeer, R.R., van den Brande, J.M., Yasin, M., Weed, D.T., Carothers Carraway, C.A., Thompson, J.F., Carraway, K.L. J. Cell. Physiol. (2005) [Pubmed]
  33. Ultrastructural localization of epithelial mucin core proteins in colorectal tissues. Winterford, C.M., Walsh, M.D., Leggett, B.A., Jass, J.R. J. Histochem. Cytochem. (1999) [Pubmed]
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