title: DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines.
abstract: DOT1L is a histone H3 lysine 79 (H3K79) methyltransferase mainly implicated in leukemia. Here we analyzed the function of DOT1L in breast cancer cells. The expression of DOT1L was up-regulated in malignant breast cancer tissues. Over-expression of DOT1L significantly increased the sphere formation and the cell migration activities of MCF7 breast cancer cell line. In contrast, knockdown of DOT1L reduced the cell migration activity of MDA-MB-231 breast cancer cell line. BCAT1, which encodes a branched-chain amino acid transaminase, was identified as one of the target genes controlled by DOT1L through the regulation of H3K79 methylation. Mechanistic investigation revealed that BCAT1 might be an important regulator responsible for DOT1L-mediated sphere formation and cell migration in breast cancer cells.
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Dulamsuren
authors.initials: D
authors.lastname: Oktyabri
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan; Molecular Therapeutic Target Research Unit, Institute for Frontier Science Initiative (InFIniti), Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishimura
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tange
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan; Molecular Therapeutic Target Research Unit, Institute for Frontier Science Initiative (InFIniti), Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan. Electronic address: suzuki-t@staff.kanazawa-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D000637:Transaminases / Q000235:genetics*
chemical_list: C473477:DOT1L protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C490590:BCAT1 protein, human; D000637:Transaminases
keywords: Cancer progression; Cell migration; Histone methyltransferase; Sphere formation; Transcriptional regulation