PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL

S. Ueno, H. Tatetsu, H. Hata, T. Iino, H. Niiro, K. Akashi, D. G. Tenen, H. Mitsuya, Y. Okuno

研究成果: ジャーナルへの寄稿記事

15 引用 (Scopus)

抄録

We earlier reported that PU.1 was downregulated in myeloma cell lines and myeloma cells in a subset of myeloma patients, and that conditional PU.1 expression in PU.1-negative myeloma cell lines, U266 and KMS12PE, induced growth arrest and apoptosis. To elucidate the molecular mechanisms of the growth arrest and apoptosis, we performed DNA microarray analyses to compare the difference in gene expression before and after PU.1 induction in U266 cells. Among cell cycle-related genes, cyclin A2, cyclin B1, CDK2 and CDK4 were downregulated and p21 was upregulated, although among apoptosis-related genes, tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) was found highly upregulated. When TRAIL was knocked down by small interference RNAs, apoptosis of PU-1-expressing cells was inhibited, suggesting that TRAIL has a critical role in PU.1-induced apoptosis in both U266 and KMS12PE myeloma cells. In both U266 and KMS12PE cells expressing PU.1, PU.1 directly bound to a region 30 bp downstream of the transcription start site of the TRAIL gene. Upregulation of PU.1-induced transactivation of the TRAIL promoter in reporter assays, and disruption of the PU.1-binding site in the TRAIL promoter eliminated this transactivation. Therefore, we conclude that PU.1 is capable of inducing apoptosis in certain myeloma cells by direct transactivation of TRAIL.

元の言語英語
ページ(範囲)4116-4125
ページ数10
ジャーナルOncogene
28
発行部数46
DOI
出版物ステータス出版済み - 11 1 2009

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TNF-Related Apoptosis-Inducing Ligand
Transcriptional Activation
Apoptosis
Cyclin A2
Down-Regulation
Cyclin B1
Cell Line
cdc Genes
Transcription Initiation Site
Microarray Analysis
Growth
RNA Interference
Oligonucleotide Array Sequence Analysis
Genes
Up-Regulation
Tumor Necrosis Factor-alpha
Binding Sites
Ligands
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

これを引用

PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL. / Ueno, S.; Tatetsu, H.; Hata, H.; Iino, T.; Niiro, H.; Akashi, K.; Tenen, D. G.; Mitsuya, H.; Okuno, Y.

:: Oncogene, 巻 28, 番号 46, 01.11.2009, p. 4116-4125.

研究成果: ジャーナルへの寄稿記事

Ueno, S, Tatetsu, H, Hata, H, Iino, T, Niiro, H, Akashi, K, Tenen, DG, Mitsuya, H & Okuno, Y 2009, 'PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL', Oncogene, 巻. 28, 番号 46, pp. 4116-4125. https://doi.org/10.1038/onc.2009.263
Ueno, S. ; Tatetsu, H. ; Hata, H. ; Iino, T. ; Niiro, H. ; Akashi, K. ; Tenen, D. G. ; Mitsuya, H. ; Okuno, Y. / PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL. :: Oncogene. 2009 ; 巻 28, 番号 46. pp. 4116-4125.
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T1 - PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL

AU - Ueno, S.

AU - Tatetsu, H.

AU - Hata, H.

AU - Iino, T.

AU - Niiro, H.

AU - Akashi, K.

AU - Tenen, D. G.

AU - Mitsuya, H.

AU - Okuno, Y.

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N2 - We earlier reported that PU.1 was downregulated in myeloma cell lines and myeloma cells in a subset of myeloma patients, and that conditional PU.1 expression in PU.1-negative myeloma cell lines, U266 and KMS12PE, induced growth arrest and apoptosis. To elucidate the molecular mechanisms of the growth arrest and apoptosis, we performed DNA microarray analyses to compare the difference in gene expression before and after PU.1 induction in U266 cells. Among cell cycle-related genes, cyclin A2, cyclin B1, CDK2 and CDK4 were downregulated and p21 was upregulated, although among apoptosis-related genes, tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) was found highly upregulated. When TRAIL was knocked down by small interference RNAs, apoptosis of PU-1-expressing cells was inhibited, suggesting that TRAIL has a critical role in PU.1-induced apoptosis in both U266 and KMS12PE myeloma cells. In both U266 and KMS12PE cells expressing PU.1, PU.1 directly bound to a region 30 bp downstream of the transcription start site of the TRAIL gene. Upregulation of PU.1-induced transactivation of the TRAIL promoter in reporter assays, and disruption of the PU.1-binding site in the TRAIL promoter eliminated this transactivation. Therefore, we conclude that PU.1 is capable of inducing apoptosis in certain myeloma cells by direct transactivation of TRAIL.

AB - We earlier reported that PU.1 was downregulated in myeloma cell lines and myeloma cells in a subset of myeloma patients, and that conditional PU.1 expression in PU.1-negative myeloma cell lines, U266 and KMS12PE, induced growth arrest and apoptosis. To elucidate the molecular mechanisms of the growth arrest and apoptosis, we performed DNA microarray analyses to compare the difference in gene expression before and after PU.1 induction in U266 cells. Among cell cycle-related genes, cyclin A2, cyclin B1, CDK2 and CDK4 were downregulated and p21 was upregulated, although among apoptosis-related genes, tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) was found highly upregulated. When TRAIL was knocked down by small interference RNAs, apoptosis of PU-1-expressing cells was inhibited, suggesting that TRAIL has a critical role in PU.1-induced apoptosis in both U266 and KMS12PE myeloma cells. In both U266 and KMS12PE cells expressing PU.1, PU.1 directly bound to a region 30 bp downstream of the transcription start site of the TRAIL gene. Upregulation of PU.1-induced transactivation of the TRAIL promoter in reporter assays, and disruption of the PU.1-binding site in the TRAIL promoter eliminated this transactivation. Therefore, we conclude that PU.1 is capable of inducing apoptosis in certain myeloma cells by direct transactivation of TRAIL.

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