論文 - 佐々木　泰史

Increased expression of T-fimbrin gene after DNA damage in CHO cells and inactivation of T-fimbrin by CpG methylation in human colorectal cancer cells.

Yasushi Sasaki, Fumio Itoh, Toshihisa Kobayashi, Takefumi Kikuchi, Hiromu Suzuki, Minoru Toyota, Kohzoh Imai

International journal of cancer   97 ( 2 ) 211 - 6  2002年01月  [査読有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

When DNA damage is induced by unprogrammed extrinsic events, activating-cell-cycle checkpoints delay cell-cycle progression in the G1 or G2 phases and allow repair of a damaged template. In this study, we evaluated changes in gene expression upon radiation-induced G2 cell-cycle arrest using Chinese hamster ovary (CHO) cells. T-fimbrin, an actin-binding protein, was overexpressed in CHO cells in which G2 arrest had been induced by X-radiation. Northern blot analysis revealed that T-fimbrin gene expression was induced not only by X-radiation but also by a topoisomerase II inhibitor, etoposide. Transfection of CHO cells with a vector encoding T-fimbrin antisense RNA demonstrated that reduced T-fimbrin expression induced alterations in cell-cycle control; radiation-induced G2 arrest was short and decreased in cells transfected with antisense T-fimbrin. Additionally, T-fimbrin gene expression was suppressed in a human colorectal cancer cell line, SW948, because of promoter-specific DNA methylation. These results suggest that downregulation of T-fimbrin may be involved in cancer development through G2/M cell-cycle control in mammalian cells.

DOI PubMed

M期チェックポイント遺伝子の異常メチル化とMicrotubule Inhibitor感受性に対する分子マーカーとしての応用

佐藤 亜由美, 豊田 実, 佐々木 泰史, 伊東 文生, 今井 浩三

日本分子腫瘍マーカー研究会誌 ( Japanese Society for Molecular Tumor Marker Research )  18   52 - 53  2002年

DOI CiNii

The p53 family member genes are involved in the Notch signal pathway.

Yasushi Sasaki, Setsuko Ishida, Ichiro Morimoto, Toshiharu Yamashita, Takashi Kojima, Chikashi Kihara, Toshihiro Tanaka, Kohzoh Imai, Yusuke Nakamura, Takashi Tokino

The Journal of biological chemistry   277 ( 1 ) 719 - 24  2001年10月  [査読有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

The p53 tumor suppressor is a transcription factor that regulates cell growth and death in response to environmental stimuli such as DNA damage. p63/p51 and p73 were recently identified as members of the p53 gene family. In contrast to p53 however, p63 and p73 are rarely mutated in human cancers. Mice that lack p53 are developmentally normal, while p63 and p73 appear to play critical roles in normal development. To determine how p63 and p73 are involved in normal development, we attempted to identify target genes that are specifically regulated by p63 and/or p73 but not by p53. We found that the Jagged1 (JAG1) and Jagged2 (JAG2) genes, encoding ligands for the Notch receptors, are up-regulated by p63 and p73. Furthermore, we identified a p63-binding site in the second intron of the JAG1 gene, which can directly interact with the p63 protein in vivo, as assessed by a chromatin immunoprecipitation assay. A heterologous reporter assay revealed that this p63-binding site is a functional response element and is specific for p63. We also found a target of Notch signaling, HES-1 was up-regulated in Jurkat cells, in which Notch1 is highly expressed, when co-cultured with p63-transfected cells, suggesting that p63 can trigger the Notch signal pathway in neighboring cells. Our findings show an association between the p53 family genes and Notch signaling and suggest a potential molecular mechanism for the involvement of the p53 family genes in normal development.

DOI DOI2 PubMed

Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer.

Sasaki Y, Morimoto I, Ishida S, Yamashita T, Imai K, Tokino T

Gene therapy   8 ( 18 ) 1401 - 1408  2001年09月  [査読有り]

担当区分：   筆頭著者

　概要を見る

p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via adenoviral vectors, and compared their effects on cell growth. Among 10 cell lines tested, six cell lines displayed a similar response following transduction of p53, p73beta or p51A/p63gamma; two lines underwent cell-cycle arrest, three lines exhibited apoptosis and one line showed no-effect following transduction. The effect on cell-cycle progression was variable in the other four cell lines. Interestingly, three cell lines were resistant to p53-mediated apoptosis, including two lines having endogenous wild-type p53 alleles, but underwent apoptosis after transduction of p73beta or p51A/p63gamma. Similar to p53, transduction of p51A/p63gamma induced extensive apoptosis when combined with adriamycin or X-radiation in SW480 cells, which are normally resistant to apoptosis. Transduction of p73beta and p51A/p63gamma also reduced the tumorigenicity of two colorectal cancer cells in vivo. These results suggest that adenovirus-mediated p73beta and p51A/p63gamma transfer are potential novel approaches for the treatment of human cancers, particularly for tumors that are resistant to p53 gene therapy.

DOI PubMed

Mutational analysis of the beta-catenin gene in gastric carcinomas.

Sasaki Y, Morimoto I, Kusano M, Hosokawa M, Itoh F, Yanagihara K, Imai K, Tokino T

Tumour biology   22 ( 2 ) 123 - 130  2001年03月  [査読有り]

担当区分：   筆頭著者

　概要を見る

Previous studies reported that mutation of the adenomatous polyposis coli (APC) gene was not observed in the majority of gastric cancers. To evaluate the role of the APC/beta-catenin/Tcf pathway, we analyzed mutations in the beta-catenin gene and the accumulation of beta-catenin protein in gastric carcinomas. An interstitial deletion spanning exon 3 of the beta-catenin gene was observed in 1 of 13 gastric cancer cell lines. No missense mutation was found in these 13 cell lines. Nuclear and/or cytoplasmic localization of beta-catenin was observed in 16 of 70 primary gastric carcinomas by immunohistochemistry, while we found no mutations in exon 3 in 35 carcinoma tissues available for PCR amplification. Our findings suggest that somatic mutations of the beta-catenin gene are rare in human gastric carcinomas and that accumulation of normal beta-catenin protein in a subset of gastric cancers may be due to other mechanisms of its activation.

DOI PubMed

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy

Yukinari Yoshida, Takao Endo, Yasushi Sasaki, Fumio Itoh, Shigeru Sasaki, Yoshiaki Arimura, Masayuki Arashi, Masanori Ohara, Masahiro Fujita, Masao Hosokawa, Kohzoh Imai

Journal of Gastroenterology ( Springer Science and Business Media LLC )  36 ( 1 ) 39 - 43  2001年01月  [査読有り]  [国際誌]

DOI PubMed

情報システムのポストゲノムプロジェクトへの応用

辰巳治之, 青木文夫, 明石浩史, 宮司正道, 豊田実, 佐々木泰史, 西森博幸, 時野隆至, 伊東文生, 今井浩三

新医療   11   64 - 69  2001年

アデノウイルスベクターを用いたp53ファミリー遺伝子導入は大腸癌由来細胞株に細胞周期停止とアポトーシスを誘導する 大腸癌の遺伝子治療への応用

佐々木泰史, 時野隆至

放射線生物研究 ( 放射線生物研究会 )  3 ( 3 ) 279 - 290  2001年  [査読有り]  [招待有り]

担当区分：   筆頭著者

CiNii

ポストゲノム・プロジェクトのアプリケーション: p53遺伝子機能解析とマルチパラレルコンピューティング

青木文夫, 辰巳治之, 明石浩史, 宮司正道, 豊田実, 佐々木泰史, 西森博幸, 時野隆至

医療とコンピュータ   12   31 - 40  2001年

Identification of genes highly expressed in G2-arrested Chinese hamster ovary cells by differential display analysis.

Sasaki Y, Itoh F, Suzuki H, Kobayashi T, Kakiuchi H, Hareyama M, Imai K

Journal of clinical laboratory analysis   14 ( 6 ) 314 - 319  2000年01月  [査読有り]

担当区分：   筆頭著者

　概要を見る

Abnormal cell cycle regulation is believed to be an important step in tumorigenesis. In mammalian cells, DNA damage commonly leads to cell cycle arrest in G2; however, little is known about the detailed biochemical mechanisms underlying the DNA damage-induced G2 arrest. In order to identify genes differentially expressed in association with G2 arrest, differential display analysis was performed between exponentially growing Chinese hamster ovary (CHO) cells and G2-arrested CHO cells induced by etoposide, SN-38, or X-radiation. We identified five cDNA clones whose expression was up-regulated in G2-arrested CHO cells. Sequence analysis revealed that three clones were homologous to known genes: isogene I of translation initiation factor eIF-4A, ribosomal protein L13, and translation repressor NAT1. The remaining two clones showed no homology to known genes. These results indicate that DNA damage can alter the expression of multiple genes, including translational regulators.

DOI PubMed

医学用語解説：Caretaker遺伝子・染色体の不安定性

小林寿久, 佐々木泰史, 伊東文生

G.I.Research   7   70 - 73  1999年  [査読有り]  [招待有り]

CiNii

The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma

S Ishida, K Yoshida, Y Kaneko, Y Tanaka, Y Sasaki, F Urano, A Umezawa, J Hata, K Fujinaga

CYTOGENETICS AND CELL GENETICS ( KARGER )  82 ( 3-4 ) 278 - 283  1998年  [査読有り]

　概要を見る

Chromosome translocation creates a fusion between the EWSR1 gene and an ETS family gene. The fusion between these two genes is a characteristic feature of Ewing sarcoma. We previously identified a fourth translocation, t(17;22)(q12;q12), in genomic DNA isolated from cells of patients affected with Ewing sarcoma. The discovery of this translocation suggested that there might be a novel EWSR1-ETV4 fusion gene. In the present study, we determined the genomic breakpoint and characterized the chimeric transcript of the EWSR1-ETV4 fusion gene in two t(17;22) Ewing sarcomas. Reverse transcriptase-PCR assay showed an in-frame fusion between the 5'-terminal region of EWSR1 and the 3' end of ETV4 (alias E1AF, PEA3); the chimeric transcript could thus serve as a template for expression of a protein composed of the N-terminal portion of EWSR1 fused to the DNA-binding domain of ETV4. Long PCR and sequence analysis of genomic DNA revealed that either exon 8 or intron 7 of EWSR 1 is fused to the same intron of ETV4 in both tumors. Several palindromic oligomer sequences were found close to the breakpoints in both genes. The 159-bp Alu-like sequence was repealed in the breakpoint region of the ETV4 gene. These observations suggest a mechanism of EWSR1-ETV4 gene fusion.

Subcapsular hematoma of the liver and pylethrombosis in the setting of cholestatic liver injury

Hirofumi Sakamoto, Mitsuo Suga, Itaru Ozeki, Toshihisa Kobayashi, Toshiaki Sugaya, Yasushi Sasaki, Naoki Azuma, Fumio Itoh, Shin-ichi Sakamoto, Akira Yachi, Kohzoh Imai

Journal of Gastroenterology ( Springer Science and Business Media LLC )  31 ( 6 ) 880 - 884  1996年11月  [国際誌]

DOI PubMed

蛋白分解酵素阻害剤メシル酸ナファモスタットの大量療法奏効した重症急性膵炎と考えられた２症例

川崎君王, 有村佳昭, 平田博巳, 鈴木隆, 角本芳隆, 村上里絵子, 金戸宏行, 佐々木泰史, 今井浩三

医薬の門   35   12 - 15  1995年  [査読有り]

大腸癌の腫瘍マーカー

佐々木泰史, 伊東文生, 日野田裕治, 今井浩三

癌の臨床   40   697 - 703  1994年  [査読有り]  [招待有り]

肝内胆管粘表皮癌の一例

佐々木泰史, 日野田裕治, 高山義一, 仲川尚明, 今井浩三, 矢花剛, 谷内昭, 榎本克彦

日本消化器病学会雑誌   88   1110 - 1115  1991年04月  [査読有り]

担当区分：   筆頭著者

PubMed

再生不良性貧血を伴う全身性エリテマトーデスと考えられる一症例

佐々木泰史, 杉山敏郎, 石田禎夫, 嶋中昭二, 細川寿和, 今井浩三, 谷内昭

日本臨床免疫学会雑誌   12 ( 4 ) 422 - 428  1989年  [査読有り]

担当区分：   筆頭著者

　概要を見る

A case of serologically highly suspected systemic lupus erythematosus (SLE) with pancytopenia because of hypoplastic bone marrow was reported. A 38 year-old female was admitted to Sapporo Medical College Hospital because of general malaise and body weight loss. On admission, laboratory examinations revealed severe pancytopenia, positive antinuclear antibody, positive anti-DNA antibodies, high titer of anti-Sm antibodies and anti-RNP antibodies, hypocomplementemia, and severe hypoplastic bone marrow. The diagnosis of SLE (three items of the 1982 revised criteria was present in this case) with aplastic anemia was highly suggested. Since a complement-dependent serum inhibitor of the growth of the patient's bone marrow cells in vitro was detected in patient's desease phase serum, it was suggested that the marrow aplasia was mediated by autoimmune mechanisms. © 1989, The Japan Society for Clinical Immunology. All rights reserved.

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