title: Involvement of B3GALNT2 overexpression in the cell growth of breast cancer.
abstract: A number of glycosyltransferases have been identified and biologically characterized in cancer cells, yet their exact pathophysiological functions are largely unknown. Here, we report the critical role of β1,3-N-acetylgalactosaminyltransferase II (B3GALNT2), which transfers N-acetylgalactosamine (GalNAc) in a β1,3 linkage to N-acetylglucosamine, in the growth of breast cancer cells. Comprehensive transcriptomics, quantitative PCR and northern blot analyses indicated this molecule to be exclusively upregulated in the majority of breast cancers. Knockdown of B3GALNT2 expression by small interfering RNA attenuated cell growth and induced apoptosis in breast cancer cells. Overexpression of B3GALNT2 in HEK293T cells prompted secretion of the gene product into the culture medium, suggesting that B3GALNT2 is potentially a secreted protein. Furthermore, we demonstrated that B3GALNT2 is N-glycosylated on both Asn-116 and Asn-174 and that this modification is necessary for its secretion in breast cancer cells. Our findings suggest that this molecule represents a promising candidate for the development of a novel therapeutic targeting drug and a potential diagnostic tumor marker for patients with breast cancer, especially TNBC.
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshimaru
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.affiliation: Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.affiliation: Department of Surgery, Tokushima Breast Care Clinic, Tokushima 770-0052, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D006031:Glycosylation; D006801:Humans; D007124:Immunoenzyme Techniques; D017350:N-Acetylgalactosaminyltransferases / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000594712:B3GALNT2 protein, human; D017350:N-Acetylgalactosaminyltransferases