Details of a Researcher - TOKINO Takashi

Misc - TOKINO Takashi

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p73転写制御因子によるIL-4シグナルの活性化

佐々木泰史, 見田裕章, 豊田実, 石田勢津子, 山下利春, 田中敏博, 中村祐輔, 今井浩三, 時野隆至

日本癌学会総会記事 63rd 2004

J-GLOBAL

造血器腫ようにおけるアポトーシス関連遺伝子のエピジェネティックな異常の解析

高橋文彦, 豊田実, 村井政史, 鈴木拓, 見田裕章, 佐々木泰史, 石田禎夫, 時野隆至, 今井浩三

日本癌学会総会記事 63rd 2004

J-GLOBAL

アクチン結合蛋白T-fimbrinによるG2/M期制御と抗癌剤感受性

佐々木泰史, 池田博, 見田裕章, 豊田実, 時野隆至, 日野田裕治, 今井浩三

日本分子生物学会年会プログラム・講演要旨集 27th 2004

J-GLOBAL

ヒト胃癌におけるナトリウムトランスポーターファミリー遺伝子SLC5A8の異常メチル化と発現抑制

上野理子, 豊田実, 秋野公臣, 見田裕章, 村井政史, 佐々木泰史, 鈴木拓, 遠藤高夫, 時野隆至

日本癌学会総会記事 63rd 2004

J-GLOBAL

Berrant methylation and gene silencing of proapoptotic genes, hrk, in gastrointestinal tumors.

F Itoh, M Toyota, T Obata, A Satoh, Y Sasaki, H Suzuki, T Tokino, JPJ Issa, K Imai

CLINICAL CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH ) 9 ( 16 ) 6160S - 6160S 2003.12

Research paper, summary (international conference)

End User指向ネットワーク対応型ゲノム解析システムの開発とその応用によるp53 family gene標的遺伝子の同定

明石浩史, 豊田実, 青木文夫, 佐々木泰史, 大西浩文, 見田裕章, 戸倉一, 苗代康可, 丸山玲緒, 中村正弘, 今井浩三, 時野隆至, 辰巳治之, 秋野豊明

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 23回 439 - 440 2003.11

Histone deacetylation, but not hypermethylation, modifies class II transactivator and MHC class II gene expression in squamous cell carcinomas.

Takayuki Kanaseki, Hideyuki Ikeda, Yukio Takamura, Minoru Toyota, Yoshihiko Hirohashi, Takashi Tokino, Tetsuo Himi, Noriyuki Sato

Journal of immunology (Baltimore, Md. : 1950) 170 ( 10 ) 4980 - 5 2003.05 [Refereed] [International journal]

In this study, we first categorized nine squamous cell carcinoma (SCC) cell lines into two groups in terms of the expression of HLA-DR, -DP, and -DQ molecules. Subsequently, the expression of class II transactivator (CIITA) was studied in these cell lines, because it is widely accepted that the expression of MHC class II molecules is regulated by different types of CIITA transcripts that are initiated by distinct promoters. The majority of the SCC cell lines (six of nine) expressed HLA-DR molecules and CIITA promoter IV (pIV) transcripts in the presence of IFN-gamma. In contrast, three of the nine SCC cell lines were completely negative for class II molecules and all types of CIITA, suggesting epigenetic changes in the promoter region in these cells. Previously, methylation of CIITA pIV was reported to silence CIITA gene expression. We extensively studied the methylation status of CIITA pIV using a panel of 22 SCC cell lines. Remarkably, none of the SCC cell lines demonstrated hypermethylation at the site. In contrast, treatment with a histone deacetylation inhibitor in combination with IFN-gamma clearly restored the expression of the CIITA type IV gene in the HLA-DR-negative SCC cell lines, and the acetylation status of histone H3 examined by chromatin immunoprecipitation analysis was closely associated with the gene expression. Moreover, stable transfection of the CIITA gene into an HLA-DR-negative cell line restored constitutive expression of MHC class II molecules. Therefore, histone deacetylation, but not hypermethylation, modifies CIITA DNA and class II gene expression in SCC.

PubMed

Bioinformaticsによるゲノム・遺伝子解析と臨床への応用

明石浩史, 豊田実, 時野隆至, 辰巳治之, 今井浩三

Drug delivery system 18 ( 3 ) 218 - 218 2003.05

CiNii

Analysis of lung tumorigenesis in chimeric mice indicates the Pulmonary adenoma resistance 2 (Par2) locus to operate in the tumor-initiation stage in a cell-autonomous manner: detection of polymorphisms in the Poli gene as a candidate for Par2.

Gang-Hong Lee, Hiroyuki Nishimori, Yasushi Sasaki, Hiroshi Matsushita, Tomoyuki Kitagawa, Takashi Tokino

Oncogene 22 ( 15 ) 2374 - 82 2003.04 [Refereed] [International journal]

The Pulmonary adenoma resistance 2 (Par2) locus of the BALB/cByJ mouse, located within 0.5 cM of chromosome 18, is responsible for reducing the mean multiplicity of urethane-induced lung tumors relative to those in C57BL/6J, A/J and C3H/HeJ mice. Thus, BALB/B6-Par2 congenic strain genetically identical to BALB/cByJ except carrying C57BL/6J Par2 alleles develops seven times more tumors than BALB/cByJ. To gain clues for identification of Par2 candidate genes, we analysed lung tumorigenesis in BALB/cByJ<-->BALB.B6-Par2 chimeric animals. Of 100 tumors induced by urethane in 16 chimeras, 82 originated from BALB.B6-Par2 cells, indicating the Par2 phenotype to be cell-autonomous. In addition, the BALB.B6-Par2- and BALB/cByJ-derived tumors were similar in mean size, implying that the phenotype is primarily expressed during initiation rather than in the promotion stage of carcinogenesis. Given these results, we surveyed a comprehensive mouse genome database and physically mapped Par2 within a 2.3 Mbp segment containing three known genes, Poli, Mbd2 and Dcc. Among those, the Poli seemed to be the most reasonable Par2 candidate, since it encodes an extremely error-prone DNA polymerase preferentially incorporating G or T opposite template T in vitro, reminiscent of the Kras2 activation because of an A to G or T point mutation within codon 61 with which most urethane-induced lung tumors are initiated. Indeed, our sequencing of Poli cDNAs from BALB/cByJ, C57BL/6J, A/J and C3H/HeJ lungs revealed 21 BALB/cByJ-specific single-nucleotide polymorphisms in the coding region accompanied by seven amino-acid substitutions and an elevated frequency of alternative splicing, while no polymorphisms associated with tumor susceptibility were found for either Mbd2 or Dcc. Notably, we obtained evidence that BALB/cByJ Par2 alleles may selectively decrease the frequency of Kras2-mutated tumors compared with C57BL/6J alleles. Consequently, the Poli is an intriguing Par2 candidate clearly deserving further evaluation.

DOI PubMed

Induction of tenascin-C by tumor-specific EWS-ETS fusion genes.

Goichi Watanabe, Hiroyuki Nishimori, Hideto Irifune, Yasushi Sasaki, Setsuko Ishida, Hitoshi Zembutsu, Toshihiro Tanaka, Satoshi Kawaguchi, Takuro Wada, Jun-ichi Hata, Moriaki Kusakabe, Koichi Yoshida, Yusuke Nakamura, Takashi Tokino

Genes, chromosomes & cancer 36 ( 3 ) 224 - 32 2003.03 [Refereed] [International journal]

Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (PNETs) are associated with a chromosomal translocation resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of an ETS transcription factor (most commonly FLI1 or ERG). Although previous reports suggested that these chimera proteins would act as aberrant transcription factors, their downstream targets have not been fully elucidated. To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line, HT-1080, by retroviral transduction. Here we report that Tenascin-C (TNC) is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal ETSs. Furthermore, through use of an antisense cDNA expression vector we show that expression of endogenous TNC mRNA and protein were reduced coordinately with attenuation of EWS-FLI1 fusion protein expression. A chromatin immunoprecipitation assay showed direct interaction between the TNC promoter and the EWS-FLI1 fusion protein in vivo. In addition, a luciferase reporter assay revealed that EWS-ETSs upregulated the TNC gene through four ETS binding sites in the TNC promoter. High levels of TNC expression were observed in a subset of ES cell lines (3 of 6) and primary tumors (4 of 6). Together with previous studies showing that TNC expression is involved in the invasive and malignant phenotype of several tumor types, our data suggest that the oncogenic effect of EWS-ETS may be mediated in part by upregulating of TNC expression.

DOI PubMed

DNA損傷により発現誘導されるタンパクt-fimbrinのG2/Mcheckpointへの関与と抗癌剤感受性

池田博, 佐々木泰史, 豊田実, 見田裕章, 時野隆至, 今井浩三

日本癌治療学会誌 38 ( 2 ) 2003

J-GLOBAL

ヒト胃癌におけるナトリウムトランスポーターファミリー遺伝子SLC5A8の異常メチル化と発現抑制

田賀理子, 豊田実, 秋野公臣, 佐藤亜由美, 見田裕章, 村井政史, 佐々木泰史, 鈴木拓, 時野隆至

日本分子生物学会年会プログラム・講演要旨集 26th 2003

J-GLOBAL

p53ファミリーの抗腫よう活性と癌治療への応用

佐々木泰史, 石田勢津子, 苗代康可, 今井浩三, 時野隆至

日本癌学会総会記事 62nd 2003