ABO Histo-Blood Groups and Cancer
- Otros grupos
- Regulatory Genomics
- Chromatin and Cell Fate
- Disease Genomics
- Epigenetic Mechanisms of Cancer and Cell Differentiation
- Cancer Genetics and Epigenetics
- Cancer and Iron
- ICO-IMPPC Joint Program - Genetic Diagnostics
- Genetic Variation and Cancer
- Genomics and Bioinformatics
- ABO Histo-Blood Groups and Cancer
- Cancer Genome Biology
One main goal of our laboratory is to examine the role and significance of altered expressions of glycosyltransferase genes in the pathogenesis and progression of cancer.
In multicellular organisms, cells are embedded within a complex network of extracellular matrices and arranged in cooperative assemblies. As parts of glycoproteins and glycolipids that play a crucial role in cell-to-cell and cell-to-extracellular matrix interactions, complex carbohydrate structures are present on the outer cell membrane. These carbohydrate structures are synthesized through glycosyltransferase actions. Cell surface carbohydrate profiles are distinctly different depending on both cell type and genotype. During cellular differentiation and maturation, these carbohydrate structures undergo various changes. Drastic changes observed during cellular transformation to malignancy often result in the loss of certain antigenic structures and/or the appearance of other antigenic structures. Also, they sometimes predict the metastatic tendency and the survival/life expectancy of patients. Consequently, the detection of tumor-specific carbohydrate antigens in serum and secretion has been used as a key method of cancer diagnosis.
We have been studying the expression of glycosyltransferase genes in breast and other types of cancer. Through our studies, we observed both an increase in the expression of several genes and a decrease in several others. Because DNA methylation alterations are one of the most frequently observed phenomena in cancer, we hypothesize that the expression of a majority of the down-regulated glycosyltransferase genes may be repressed by DNA methylation of their promoter regions. Alternatively, decreased expression may be caused by diminished expression of transcription factor genes that transcribe glycosyltransferase genes. Similarly, the up-regulation of the other glycosyltransferase genes may be mediated by the enhanced expression of different transcription factor genes. Through our continuing research, we will investigate these possibilities and elucidate the molecular mechanisms that underlie the differential and individualized facial complexion of cancer cells.
Figure 1. Systematic Multiplex RT-PCR of RNA from human tissues SM RT-PCR was performed to determine the expression of 68 glycosyltransferase genes, using RNA from 27 different human tissues. Reaction products were analyzed by polyacrylamide gel electrophoresis. Genomic DNA from 2 individuals was used as the control template, and the results are shown in lanes G1 and G2. The following symbols are used to represent tissue names in the experiments: SK (skin), SM (skeletal muscle), BN (brain cerebrum), BC (brain cerebellum), BM (bone marrow), SP (spleen), TH (thymus), TR (trachea), LU (Lung), PA (parotid gland), SG (salivary gland), ST (stomach), CO (colon), RE (rectum), TG (thyroid gland), AG (adrenal gland), KI (kidney), BL (bladder), PE (penis), PR (prostate), TE (testis), VU (vulva), CE (cervix), UT (uterus), OV (ovary), PL (placenta), and BR (breast). M denotes the molecular size marker. The expected locations of the amplified DNA fragments are shown on the left side of the figure.
Figure 2. Hierarchical clustering of expression data
The Excel dataset was imported into the GeneSpring software, and the relationships among tissues and genes were analyzed using a hierarchical clustering algorithm. The dendrogram at the top of the panel indicates the degrees of relationship among different tissues, and the dendrogram at the left indicates the degrees of relationship among different glycosyltransferase genes regarding gene expression.
For more information on the ABO Blood Group System, please see Dr. Yamamoto's pages at:
Cid E, Yamamoto M, Buschbeck M, Yamamoto F. Murine cell glycolipids customization by modular expression of glycosyltransferases. PLoS ONE 2013; 8(6): e64728
Yamamoto M, Cid E, Yamamoto F. Molecular genetic basis of the human Forssman glycolipid antigen negativity. Sci Rep 2012; 2: 975
Yamamoto F, Cid E, Yamamoto M, Blancher A. ABO research in the modern era of genomics. Transfus Med Rev 2012 Apr; 26(2): 103-18
Yamamoto M, Cid E, Bru S, Yamamoto F. Rare and frequent promoter methylation, respectively, of TSHZ2 and 3 genes that are both downregulated in expression in breast and prostate cancers. PLoS ONE 2011; 6(3): e17149
Yamamoto F, Yamamoto M, Blancher A. Generation of histo-blood group B transferase by replacing the N-acetyl-D-galactosamine recognition domain of human A transferase with the galactose-recognition domain of evolutionarily related murine alpha1,3-galactosyltransferase. Transfusion 2010 Mar; 50(3): 622-30
Yamamoto F, Yamamoto M. Identification of genes that exhibit changes in expression on the 8p chromosomal arm by the Systematic Multiplex RT-PCR (SM RT-PCR) and DNA microarray hybridization methods. Gene Expr. 2008; 14(4): 217-27
Yamamoto F, Yamamoto M. Scanning copy number and gene expression on the 18q21-qter chromosomal region by the systematic multiplex PCR and reverse transcription-PCR methods. Electrophoresis 2007 Jun; 28(12): 1882-95
Yamamoto F. Review: ABO blood group system--ABH oligosaccharide antigens, anti-A and anti-B, A and B glycosyltransferases, and ABO genes. Immunohematology 2004; 20(1): 3-22
Yamamoto M, Takai D, Yamamoto F. Comprehensive expression profiling of highly homologous 39 hox genes in 26 different human adult tissues by the modified systematic multiplex RT-pCR method reveals tissue-specific expression pattern that suggests an important role of chromosomal structure in the regulation of hox gene expression in adult tissues. Gene Expr. 2003; 11(3): 199-210
Yamamoto M, Yamamoto F, Luong TT, Williams T, Kominato Y. Expression profiling of 68 glycosyltransferase genes in 27 different human tissues by the systematic multiplex reverse transcription-polymerase chain reaction method revealed clustering of sexually related tissues in hierarchical clustering algorithm analysis. Electrophoresis 2003 Jul; 24(14): 2295-307
Yamamoto F, Yamamoto M, Soto JL, Kojima E, Wang EN, Perucho M, Sekiya T, Yamanaka H. Notl-Msell methylation-sensitive amplied fragment length polymorhism for DNA methylation analysis of human cancers. Electrophoresis 2001 Jun; 22(10): 1946-56
Yamamoto F, Yamamoto M. Molecular genetic basis of porcine histo-blood group AO system. Blood 2001 May; 97(10): 3308-10
Yamamoto M, Lin XH, Kominato Y, Hata Y, Noda R, Saitou N, Yamamoto F. Murine equivalent of the human histo-blood group ABO gene is a cis-AB gene and encodes a glycosyltransferase with both A and B transferase activity. J. Biol. Chem. 2001 Apr; 276(17): 13701-8
Saitou N, Yamamoto F. Evolution of primate ABO blood group genes and their homologous genes. Mol. Biol. Evol. 1997 Apr; 14(4): 399-411
Yamamoto F, McNeill PD. Amino acid residue at codon 268 determines both activity and nucleotide-sugar donor substrate specificity of human histo-blood group A and B transferases. In vitro mutagenesis study. J. Biol. Chem. 1996 May; 271(18): 10515-20
Kominato Y, McNeill PD, Yamamoto M, Russell M, Hakomori S, Yamamoto F. Animal histo-blood group ABO genes. Biochem. Biophys. Res. Commun. 1992 Nov; 189(1): 154-64
Yamamoto F, Clausen H, White T, Marken J, Hakomori S. Molecular genetic basis of the histo-blood group ABO system. Nature 1990 May; 345(6272): 229-33
Yamamoto F, Marken J, Tsuji T, White T, Clausen H, Hakomori S. Cloning and characterization of DNA complementary to human UDP-GalNAc: Fuc alpha 1----2Gal alpha 1----3GalNAc transferase (histo-blood group A transferase) mRNA. J. Biol. Chem. 1990 Jan; 265(2): 1146-51