Abstract
Enhanced fucosyltransferase IV (FUT4) expression correlates with increased tumor malignancy in many carcinomas. However, little is known about the regulation of FUT4 expression, and whether FUT4 expression is influenced by the methylation status of the FUT4 promoter is unclear. In this study, we demonstrated that FUT4 expression is negatively correlated with the methylation degree of a CpG island in the FUT4 promoter, suggesting that the methylation status of FUT4 promoter regulates the expression of FUT4. The results indicate that manipulating the methylation status of the FUT4 promoter to regulate FUT4 expression may be a novel approach in the treatment of malignant tumors.
Electronic Supplementary Material
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Key words: Fucosyltransferase, FUT4 promoter, Methylation, A431 cells, SCC12 cells
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Abbreviations used
- BSP
bisulfite sequencing PCR
- FUT4
fucosyltransferase IV
- MSP
methylation-specific PCR
- SCC
squamous carcinoma cell
- 5-aza-dC
5-aza-2-deoxycytidine
References
- 1.Martin-Satue M., Marrugat R., Cancelas J.A., Blanco J. Enhanced expression of alpha(1,3)-fucosyltransferase genes correlates with E-selectinmediated adhesion and metastatic potential of human lung adenocarcinoma cells. Cancer Res. 1998;58:1544–1550. [PubMed] [Google Scholar]
- 2.Wang X., Gu J., Ihara H., Miyoshi E., Honke K., Taniguchi N. Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling. J. Biol. Chem. 2006;281:2572–2577. doi: 10.1074/jbc.M510893200. [DOI] [PubMed] [Google Scholar]
- 3.Javaud C., Dupuy F., Maftah A., Julien R., Petit J.M. The fucosyltransferase gene family: an amazing summary of the underlying mechanisms of gene evolution. Genetica. 2003;118:157–170. [PubMed] [Google Scholar]
- 4.Madjd Z., Parsons T., Watson N.F., Spendlove I., Ellis I., Durrant L.G. High expression of Lewis y/b antigens is associated with decreased survival in lymph node negative breast carcinomas. Breast Cancer Res. 2005;7:R780–787. doi: 10.1186/bcr1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Miyoshi E., Moriwaki K., Nakagawa T. Biological function of fucosylation in cancer biology. J. Biochem. 2008;143:725–729. doi: 10.1093/jb/mvn011. [DOI] [PubMed] [Google Scholar]
- 6.Fukushima K., Satoh T., Baba S., Yamashita K. alpha1,2-Fucosylated and beta-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer. Glycobiology. 2010;20:452–460. doi: 10.1093/glycob/cwp197. [DOI] [PubMed] [Google Scholar]
- 7.Petretti T., Schulze B., Schlag P.M., Kemmner W. Altered mRNA expression of glycosyltransferases in human gastric carcinomas. Biochim. Biophys. Acta. 1999;1428:209–218. doi: 10.1016/s0304-4165(99)00080-x. [DOI] [PubMed] [Google Scholar]
- 8.Ciolczyk-Wierzbicka D., Bodzioch M., Gil D., Zmudzinska D., Dembinska-Kiec A., Laidler P. Expression of fucosyltransferases contributes to melanoma invasive phenotype. Med. Chem. 2007;3:418–424. doi: 10.2174/157340607781745401. [DOI] [PubMed] [Google Scholar]
- 9.Stirewalt D.L., Meshinchi S., Kopecky K.J., Fan W., Pogosova-Agadjanyan E.L., Engel J.H., Cronk M.R., Dorcy K.S., McQuary A.R., Hockenbery D., Wood B., Heimfeld S., Radich J.P. Identification of genes with abnormal expression changes in acute myeloid leukemia. Genes Chromosomes Cancer. 2008;47:8–20. doi: 10.1002/gcc.20500. [DOI] [PubMed] [Google Scholar]
- 10.Zhang Z., Sun P., Liu J., Fu L., Yan J., Liu Y., Yu L., Wang X., Yan Q. Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth. Biochim. Biophys. Acta. 2008;1783:287–296. doi: 10.1016/j.bbamcr.2007.10.007. [DOI] [PubMed] [Google Scholar]
- 11.Yang X., Zhang Z., Jia S., Liu Y., Wang X., Yan Q. Overexpression of fucosyltransferase IV in A431 cell line increases cell proliferation. Int. J. Biochem. Cell Biol. 2007;39:1722–1730. doi: 10.1016/j.biocel.2007.04.024. [DOI] [PubMed] [Google Scholar]
- 12.Gupta A., Godwin A.K., Vanderveer L., Lu A., Liu J. Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma. Cancer Res. 2003;63:664–673. [PubMed] [Google Scholar]
- 13.Wu H., Chen Y., Liang J., Shi B., Wu G., Zhang Y., Wang D., Li R., Yi X., Zhang H., Sun L., Shang Y. Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature. 2005;438:981–987. doi: 10.1038/nature04225. [DOI] [PubMed] [Google Scholar]
- 14.Kannagi R., Yin J., Miyazaki K., Izawa M. Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants—Hakomori’s concepts revisited. Biochim. Biophys. Acta. 2008;1780:525–531. doi: 10.1016/j.bbagen.2007.10.007. [DOI] [PubMed] [Google Scholar]
- 15.Kawamura Y.I., Toyota M., Kawashima R., Hagiwara T., Suzuki H., Imai K., Shinomura Y., Tokino T., Kannagi R., Dohi T. DNA hypermethylation contributes to incomplete synthesis of carbohydrate determinants in gastrointestinal cancer. Gastroenterology. 2008;135:142–151. doi: 10.1053/j.gastro.2008.03.031. [DOI] [PubMed] [Google Scholar]
- 16.Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J. Mol. Biol. 1987;196:261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
- 17.Serpa J., Mesquita P., Mendes N., Oliveira C., Almeida R., Santos-Silva F., Reis C.A., LePendu J., David L. Expression of Lea in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation. Cancer Lett. 2006;242:191–197. doi: 10.1016/j.canlet.2005.11.009. [DOI] [PubMed] [Google Scholar]
- 18.Syrbe U., Jennrich S., Schottelius A., Richter A., Radbruch A., Hamann A. Differential regulation of P-selectin ligand expression in naive versus memory CD4+ T cells: evidence for epigenetic regulation of involved glycosyltransferase genes. Blood. 2004;104:3243–3248. doi: 10.1182/blood-2003-09-3047. [DOI] [PubMed] [Google Scholar]
- 19.Moriwaki K., Narisada M., Imai T., Shinzaki S., Miyoshi E. The effect of epigenetic regulation of fucosylation on TRAIL-induced apoptosis. Glycoconj. J. 2010;27:649–659. doi: 10.1007/s10719-010-9310-5. [DOI] [PubMed] [Google Scholar]
- 20.Withers D.A., Hakomori S.I. Human alpha (1,3)-fucosyltransferase IV (FUTIV) gene expression is regulated by elk-1 in the U937 cell line. J. Biol. Chem. 2000;275:40588–40593. doi: 10.1074/jbc.M007262200. [DOI] [PubMed] [Google Scholar]
- 21.Taniguchi A., Suga R., Matsumoto K. Expression and transcriptional regulation of the human alpha1, 3-fucosyltransferase 4 (FUT4) gene in myeloid and colon adenocarcinoma cell lines. Biochem. Biophys. Res. Commun. 2000;273:370–376. doi: 10.1006/bbrc.2000.2929. [DOI] [PubMed] [Google Scholar]
- 22.Moro-Rodriguez E., Alvarez-Fernandez E. Losses of expression of the antigens A, Lea and Lex and over-expression of Ley in carcinomas and HGSIL of the uterine cervix. Diagn. Pathol. 2008;3:38. doi: 10.1186/1746-1596-3-38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Escrevente C., Machado E., Brito C., Reis C.A., Stoeck A., Runz S., Marme A., Altevogt P., Costa J. Different expression levels of alpha3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines. Int. J. Oncol. 2006;29:557–566. [PubMed] [Google Scholar]
- 24.Inufusa H., Adachi T., Kiyokawa T., Nakatani Y., Wakano T., Nakamura M., Okuno K., Shiozaki H., Yamamoto S., Suzuki M., Ando O., Kurimoto M., Miyake M., Yasutomi M. Ley glycolipid-recognizing monoclonal antibody inhibits procoagulant activity and metastasis of human adenocarcinoma. Int. J. Oncol. 2001;19:941–946. doi: 10.3892/ijo.19.5.941. [DOI] [PubMed] [Google Scholar]
- 25.Thurin M., Kieber-Emmons T. SA-Lea and tumor metastasis: the old prediction and recent findings. Genes Chromosomes Cancer. 2002;21:111–116. doi: 10.1089/153685902317401708. [DOI] [PubMed] [Google Scholar]
- 26.Wei J., Cui L., Liu F., Fan Y., Lang R., Gu F., Guo X., Tang P., Fu L. E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Int. J. Surg. Pathol. 2010;18:193–200. doi: 10.1177/1066896908320832. [DOI] [PubMed] [Google Scholar]
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