Abstract
Background—The intestinal epithelium is covered by a continuous layer of mucus which is secreted by well differentiated epithelial cells. Disregulation of the expression of mucins has been reported to have possible implications in the neoplastic process which affects intestinal mucosae. It is well known that preneoplastic and neoplastic tissues can express fetal phenotypic characteristics. Aims—To assess whether the expression of mucin genes in the intestinal tract is linked to the stage of cellular differentiation and tissue development, by studying the expression of six mucin genes in human fetal small intestine and colon, and also adult tissues. Methods—In situ hybridisation was used to study mRNA expression of MUC2, MUC3, MUC4, MUC5B, MUC5AC, and MUC6 in 32 human embryos and fetuses (6.5-27 weeks gestation). Normal adult mucosae were used as controls. Results—Three mucin genes, MUC2, MUC4, and MUC5AC, were differently expressed in fetal intestine compared with expression in normal adults. Conclusion—These differences in mucin gene expression suggest a possible regulatory role for these products in intestinal epithelial cell differentiation.
Keywords: mucin genes; mucins; intestine; differentiation; human fetus
Full Text
The Full Text of this article is available as a PDF (191.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aubert J. P., Porchet N., Crepin M., Duterque-Coquillaud M., Vergnes G., Mazzuca M., Debuire B., Petitprez D., Degand P. Evidence for different human tracheobronchial mucin peptides deduced from nucleotide cDNA sequences. Am J Respir Cell Mol Biol. 1991 Aug;5(2):178–185. doi: 10.1165/ajrcmb/5.2.178. [DOI] [PubMed] [Google Scholar]
- Audie J. P., Janin A., Porchet N., Copin M. C., Gosselin B., Aubert J. P. Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization. J Histochem Cytochem. 1993 Oct;41(10):1479–1485. doi: 10.1177/41.10.8245407. [DOI] [PubMed] [Google Scholar]
- Bara J., Gautier R., Daher N., Zaghouani H., Decaens C. Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae. Cancer Res. 1986 Aug;46(8):3983–3989. [PubMed] [Google Scholar]
- Bara J., Nardelli J., Gadenne C., Prade M., Burtin P. Differences in the expression of mucus-associated antigens between proximal and distal human colon adenocarcinomas. Br J Cancer. 1984 Apr;49(4):495–501. doi: 10.1038/bjc.1984.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bobek L. A., Tsai H., Biesbrock A. R., Levine M. J. Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7). J Biol Chem. 1993 Sep 25;268(27):20563–20569. [PubMed] [Google Scholar]
- Boland C. R., Montgomery C. K., Kim Y. S. A cancer-associated mucin alteration in benign colonic polyps. Gastroenterology. 1982 Apr;82(4):664–672. [PubMed] [Google Scholar]
- Boland C. R., Montgomery C. K., Kim Y. S. Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2051–2055. doi: 10.1073/pnas.79.6.2051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma. Gastroenterology. 1996 Jan;110(1):84–91. doi: 10.1053/gast.1996.v110.pm8536891. [DOI] [PubMed] [Google Scholar]
- Chambers J. A., Hollingsworth M. A., Trezise A. E., Harris A. Developmental expression of mucin genes MUC1 and MUC2. J Cell Sci. 1994 Feb;107(Pt 2):413–424. doi: 10.1242/jcs.107.2.413. [DOI] [PubMed] [Google Scholar]
- Chang S. K., Dohrman A. F., Basbaum C. B., Ho S. B., Tsuda T., Toribara N. W., Gum J. R., Kim Y. S. Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer. Gastroenterology. 1994 Jul;107(1):28–36. doi: 10.1016/0016-5085(94)90057-4. [DOI] [PubMed] [Google Scholar]
- Cheng H., Leblond C. P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat. 1974 Dec;141(4):537–561. doi: 10.1002/aja.1001410407. [DOI] [PubMed] [Google Scholar]
- Cheng H. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. II. Mucous cells. Am J Anat. 1974 Dec;141(4):481–501. doi: 10.1002/aja.1001410404. [DOI] [PubMed] [Google Scholar]
- Coapman R. A., Cooper H. S. Peanut lectin binding sites in human fetal colon. Arch Pathol Lab Med. 1986 Feb;110(2):124–127. [PubMed] [Google Scholar]
- Filipe M. I., Fenger C. Histochemical characteristics of mucins in the small intestine. A comparative study of normal mucosa, benign epithelial tumours and carcinoma. Histochem J. 1979 May;11(3):277–287. doi: 10.1007/BF01005027. [DOI] [PubMed] [Google Scholar]
- Filipe M. I. Mucins in the human gastrointestinal epithelium: a review. Invest Cell Pathol. 1979 Jul-Sep;2(3):195–216. [PubMed] [Google Scholar]
- Gendler S., Taylor-Papadimitriou J., Duhig T., Rothbard J., Burchell J. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem. 1988 Sep 15;263(26):12820–12823. [PubMed] [Google Scholar]
- Gold D., Miller F. Chemical and immunological differences between normal and tumoral colonic mucoprotein antigen. Nature. 1975 May 1;255(5503):85–87. doi: 10.1038/255085a0. [DOI] [PubMed] [Google Scholar]
- Grand R. J., Watkins J. B., Torti F. M. Development of the human gastrointestinal tract. A review. Gastroenterology. 1976 May;70(5 PT1):790–810. [PubMed] [Google Scholar]
- Gum J. R., Byrd J. C., Hicks J. W., Toribara N. W., Lamport D. T., Kim Y. S. Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism. J Biol Chem. 1989 Apr 15;264(11):6480–6487. [PubMed] [Google Scholar]
- Gum J. R., Hicks J. W., Swallow D. M., Lagace R. L., Byrd J. C., Lamport D. T., Siddiki B., Kim Y. S. Molecular cloning of cDNAs derived from a novel human intestinal mucin gene. Biochem Biophys Res Commun. 1990 Aug 31;171(1):407–415. doi: 10.1016/0006-291x(90)91408-k. [DOI] [PubMed] [Google Scholar]
- Guyonnet Duperat V., Audie J. P., Debailleul V., Laine A., Buisine M. P., Galiegue-Zouitina S., Pigny P., Degand P., Aubert J. P., Porchet N. Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes? Biochem J. 1995 Jan 1;305(Pt 1):211–219. doi: 10.1042/bj3050211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hertzog P. J., Pilbrow S. J., Pedersen J., Polglase A. L., Lawson M., Linnane A. W. Aberrant expression of intestinal mucin antigens associated with colorectal carcinoma defined by a panel of monoclonal antibodies. Br J Cancer. 1991 Nov;64(5):799–808. doi: 10.1038/bjc.1991.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hertzog P. J., Robinson H. C., Ma J., Mackay I. R., Linnane A. W. Oncofetal expression of the human intestinal mucin glycoprotein antigens in gastrointestinal epithelium defined by monoclonal antibodies. Int J Cancer. 1991 May 30;48(3):355–363. doi: 10.1002/ijc.2910480308. [DOI] [PubMed] [Google Scholar]
- Ho S. B., Kim Y. S. Carbohydrate antigens on cancer-associated mucin-like molecules. Semin Cancer Biol. 1991 Dec;2(6):389–400. [PubMed] [Google Scholar]
- Ho S. B., Niehans G. A., Lyftogt C., Yan P. S., Cherwitz D. L., Gum E. T., Dahiya R., Kim Y. S. Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res. 1993 Feb 1;53(3):641–651. [PubMed] [Google Scholar]
- Kim Y. S., Yuan M., Itzkowitz S. H., Sun Q. B., Kaizu T., Palekar A., Trump B. F., Hakomori S. Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. Cancer Res. 1986 Nov;46(11):5985–5992. [PubMed] [Google Scholar]
- Lan M. S., Batra S. K., Qi W. N., Metzgar R. S., Hollingsworth M. A. Cloning and sequencing of a human pancreatic tumor mucin cDNA. J Biol Chem. 1990 Sep 5;265(25):15294–15299. [PubMed] [Google Scholar]
- Lesuffleur T., Porchet N., Aubert J. P., Swallow D., Gum J. R., Kim Y. S., Real F. X., Zweibaum A. Differential expression of the human mucin genes MUC1 to MUC5 in relation to growth and differentiation of different mucus-secreting HT-29 cell subpopulations. J Cell Sci. 1993 Nov;106(Pt 3):771–783. doi: 10.1242/jcs.106.3.771. [DOI] [PubMed] [Google Scholar]
- Lesuffleur T., Roche F., Hill A. S., Lacasa M., Fox M., Swallow D. M., Zweibaum A., Real F. X. Characterization of a mucin cDNA clone isolated from HT-29 mucus-secreting cells. The 3' end of MUC5AC? J Biol Chem. 1995 Jun 9;270(23):13665–13673. doi: 10.1074/jbc.270.23.13665. [DOI] [PubMed] [Google Scholar]
- Lesuffleur T., Zweibaum A., Real F. X. Mucins in normal and neoplastic human gastrointestinal tissues. Crit Rev Oncol Hematol. 1994 Dec;17(3):153–180. doi: 10.1016/1040-8428(94)90053-1. [DOI] [PubMed] [Google Scholar]
- Moxey P. C., Trier J. S. Specialized cell types in the human fetal small intestine. Anat Rec. 1978 Jul;191(3):269–285. doi: 10.1002/ar.1091910302. [DOI] [PubMed] [Google Scholar]
- Podolsky D. K., Fournier D. A., Lynch K. E. Human colonic goblet cells. Demonstration of distinct subpopulations defined by mucin-specific monoclonal antibodies. J Clin Invest. 1986 Apr;77(4):1263–1271. doi: 10.1172/JCI112429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porchet N., Nguyen V. C., Dufosse J., Audie J. P., Guyonnet-Duperat V., Gross M. S., Denis C., Degand P., Bernheim A., Aubert J. P. Molecular cloning and chromosomal localization of a novel human tracheo-bronchial mucin cDNA containing tandemly repeated sequences of 48 base pairs. Biochem Biophys Res Commun. 1991 Mar 15;175(2):414–422. doi: 10.1016/0006-291x(91)91580-6. [DOI] [PubMed] [Google Scholar]
- Potten C. S., Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990 Dec;110(4):1001–1020. doi: 10.1242/dev.110.4.1001. [DOI] [PubMed] [Google Scholar]
- Shankar V., Gilmore M. S., Elkins R. C., Sachdev G. P. A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization. Biochem J. 1994 Jun 1;300(Pt 2):295–298. doi: 10.1042/bj3000295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siddiqui J., Abe M., Hayes D., Shani E., Yunis E., Kufe D. Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2320–2323. doi: 10.1073/pnas.85.7.2320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stauffer A., Lallemand A., Gaillard D. Histochimie des mucines du tube digestif chez le foetus humain. Gastroenterol Clin Biol. 1990;14(6-7):561–566. [PubMed] [Google Scholar]
- Toribara N. W., Roberton A. M., Ho S. B., Kuo W. L., Gum E., Hicks J. W., Gum J. R., Jr, Byrd J. C., Siddiki B., Kim Y. S. Human gastric mucin. Identification of a unique species by expression cloning. J Biol Chem. 1993 Mar 15;268(8):5879–5885. [PubMed] [Google Scholar]
- Yan P. S., Ho S. B., Itzkowitz S. H., Byrd J. C., Siddiqui B., Kim Y. S. Expression of native and deglycosylated colon cancer mucin antigens in normal and malignant epithelial tissues. Lab Invest. 1990 Nov;63(5):698–706. [PubMed] [Google Scholar]
- Yolken R. H., Ojeh C., Khatri I. A., Sajjan U., Forstner J. F. Intestinal mucins inhibit rotavirus replication in an oligosaccharide-dependent manner. J Infect Dis. 1994 May;169(5):1002–1006. doi: 10.1093/infdis/169.5.1002. [DOI] [PubMed] [Google Scholar]