[Regulation of human β-1,4-galactosyltransferase V gene expression in cancer cells].
β-1,4-Galactosyltransferase (β-1,4-GalT) V - whose human and mouse genes were cloned by us - has been suggested to be involved in the biosyntheses of N-glycans, O-glycans, and lactosylceramide by in vitro studies. Our recent study showed that β-1,4-GalT V-knockout mice are embryonic lethal, suggesting the importance of the glycans synthesized by β-1,4-GalT V for embryonic development. A subsequent study showed that murine β-1,4-GalT V is involved in the biosynthesis of lactosylceramide. It is well known that the glycosylation of cell surface glycoproteins and glycolipids changes dramatically upon the malignant transformation of cells. We found that among six β-1,4-GalTs the gene expression of only β-1,4-GalT V increases upon malignant transformation. The expression of the β-1,4-GalT V gene has been shown to be regulated by transcription factors Sp1 and Ets-1 in cancer cells. Both transcription factors regulate the gene expression levels of not only glycosyltransferases, but also key molecules involved in tumor growth, invasion and metastasis. Therefore, the abnormal glycosylation and malignant phenotypes of cancer cells are considered to be suppressed by regulating the expression levels of the transcription factor genes. This review gives a summary account of the gene discovery, in vivo function, and transcriptional mechanism of β-1,4-GalT V. Also, a perspective on applications of the manipulation of transcription factor genes to cancer therapy will be discussed.
Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Niigata, Japan. taksato@vos.nagaokaut.ac.jp
Takeshi
T
Sato
Kiyoshi
K
Furukawa
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005700:Galactosyltransferases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006017:Glycolipids / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007790:Lactosylceramides / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011134:Polysaccharides / Q000096:biosynthesis; D050784:Proto-Oncogene Protein c-ets-1 / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000502:physiology; D014158:Transcription, Genetic
D015703:Antigens, CD; D006017:Glycolipids; D007790:Lactosylceramides; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D050784:Proto-Oncogene Protein c-ets-1; D016329:Sp1 Transcription Factor; C009744:CDw17 antigen; D005700:Galactosyltransferases; C419408:beta-1,4-galactosyltransferase V