DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines

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 a...

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Veröffentlicht in:Biochimie 2016-04, Vol.123, p.20-31
Hauptverfasser: Oktyabri, Dulamsuren, Ishimura, Akihiko, Tange, Shoichiro, Terashima, Minoru, Suzuki, Takeshi
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container_issue
container_start_page 20
container_title Biochimie
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creator Oktyabri, Dulamsuren
Ishimura, Akihiko
Tange, Shoichiro
Terashima, Minoru
Suzuki, Takeshi
description 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. •DOT1L histone methyltransferase is up-regulated in malignant breast cancers.•DOT1L is involved in sphere formation and cell migration of breast cancer cell lines.•DOT1L regulates the expression of BCAT1 through histone H3K79 methylation.•BCAT1 is responsible for DOT1L-mediated cell migration and sphere formation.
doi_str_mv 10.1016/j.biochi.2016.01.005
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subjects Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer progression
Cell Line, Tumor
Cell migration
Female
Gene Expression Regulation
Histone methyltransferase
Humans
Methylation
Methyltransferases - metabolism
Neoplasm Metastasis
Sphere formation
Transaminases - genetics
Transcriptional regulation
title DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines
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