2003 Fiscal Year Annual Research Report

DNA障害による癌細胞応答からみた新規分子標的の探索

Research Project

Project/Area Number	13218132
Research Institution	University of Occupational and Environmental Health, Japan
Principal Investigator	河野公俊産業医科大学, 医学部, 教授 (00153479)
Keywords	シスプラチン / 薬剤耐性 / YB-1 / mtTFA / ATF4 / CTF2 / p53 / アポトーシス
Research Abstract	DNA障害による癌細胞応答からみた新規分子標的の探索を目指して、(1)DNA障害で発現誘導される分子群の解析と(2)DNA損傷センサー分子と損傷DNA認識分子の分子会合の2つの面から検討した。本研究では、DNA損傷シグナルを誘導するシスプラチンを用いた。シスプラチンで発現誘導されるか、もしくはシスプラチン耐性細胞で高発現している転写因子YB-1をはじめCTF2、mtTFA、ATF4、ZNF143を見いだした。これらの分子の中には、相互に発現を制御するだけでなく、自身がDNA損傷を認識できることも証明した。一部の転写因子は、細胞内pHやレドックスを制御し、抗アポトーシスに関与していた。次に、DNA損傷センサー分子と損傷DNA認識分子との間の新しい分子会合の存在を示した。上記の転写因子の一部は、癌抑制遺伝子産物であるp53/p73と分子会合をする。今回CTF2とp53/p73の分子会合が損傷認識分子の代表であるHMG1の遺伝子発現を制御することを示した。また、ミトコンドリア転写因子であるmtTFAがアポトーシスに伴いミトコンドリアに移行したp53と分子会合することを示した。以上、DNA損傷シグナルに伴うゲノム応答に、損傷DNAを認識する転写因子の癌特異的な分子会合と転写因子間の制御サーキット機構が関与し、新しい分子標的の可能性が示された。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Y.Oda: "Nuclear expression of Y-box-binding Protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma"J.Pathol.. 199・2. 251-258 (2003)
[Publications] H.Saji: "Nuclear expression of YB-1 protein corerlates with P-glycoprotein expression in human breast carcinoma"Cancer Lett.. 190・2. 191-197 (2003)
[Publications] H.Uramoto: "Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression"Biochem.J.. 371・Pt2. 301-310 (2003)
[Publications] M.Kuwano: "The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies"Cancer Sci.. 94・1. 9-14 (2003)
[Publications] K.Onitsuka: "Prognostic significance of UDP-N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyltransferase-3(GalNAc-T3) expression in patients with gastric carcinoma"Cancer Sci.. 94・1. 32-36 (2003)
[Publications] K.Kohno: "The pleiotropic functions of the Y-box-binding Protein, YB-1"Bioessays. 25・7. 691-698 (2003)
[Publications] Y.Yoshida: "p53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA"Cancer Res.. 63・13. 3729-3734 (2003)
[Publications] H.Izumi: "Structural and functional characterization of two human V-ATPase subunit gene promoters"Biochim.Biophys.Acta. 1628・2. 97-104 (2003)
[Publications] H.Izumi: "p300/CBP-associated factor (P/CAF) interacts with nuclear respiratory factor-1 to regulate the UDP-N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyltransferase-3 gene"Biochem.J.. 373・Pt3. 713-722 (2003)
[Publications] T.Torigoe: "Low pH enhances Sp1 DNA binding activity and interaction with TBP"Nucleic Acids Res.. 31・15. 4523-4530 (2003)
[Publications] H.Izumi: "Cellular pH regulators : potentially promising molecular targets for cancer chemotherapy"Cancer Treat.Rev.. 29・6. 541-549 (2003)
[Publications] M.Tanabe: "Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines"Cancer Res.. 63・24. 8592-8595 (2003)
[Publications] S.Yamamoto: "Expression of uridine diphosphate N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyl transferase 3 in adenocarcinoma of the pancreas"Pathobiology. 71・1. 12-18 (2004)
[Publications] C.Gu: "Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma : impact on poor prognosis and early recurrence"Br.J.Cancer. 90・2. 436-442 (2004)
[Publications] T.Fukuda: "Characterization of the 5'-untranslated region of YB-1 mRNA and autoregulation of translation by YB-1 protein"Nucleic Acids Res.. 32・2. 611-622 (2004)

2003 Fiscal Year Annual Research Report

DNA障害による癌細胞応答からみた新規分子標的の探索

Principal Investigator

河野 公俊 産業医科大学, 医学部, 教授 (00153479)

Research Products

[Publications] Y.Oda: "Nuclear expression of Y-box-binding Protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma"J.Pathol.. 199・2. 251-258 (2003)

[Publications] H.Saji: "Nuclear expression of YB-1 protein corerlates with P-glycoprotein expression in human breast carcinoma"Cancer Lett.. 190・2. 191-197 (2003)

[Publications] H.Uramoto: "Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression"Biochem.J.. 371・Pt2. 301-310 (2003)

[Publications] M.Kuwano: "The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies"Cancer Sci.. 94・1. 9-14 (2003)

[Publications] K.Onitsuka: "Prognostic significance of UDP-N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyltransferase-3(GalNAc-T3) expression in patients with gastric carcinoma"Cancer Sci.. 94・1. 32-36 (2003)

[Publications] K.Kohno: "The pleiotropic functions of the Y-box-binding Protein, YB-1"Bioessays. 25・7. 691-698 (2003)

[Publications] Y.Yoshida: "p53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA"Cancer Res.. 63・13. 3729-3734 (2003)

[Publications] H.Izumi: "Structural and functional characterization of two human V-ATPase subunit gene promoters"Biochim.Biophys.Acta. 1628・2. 97-104 (2003)

[Publications] H.Izumi: "p300/CBP-associated factor (P/CAF) interacts with nuclear respiratory factor-1 to regulate the UDP-N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyltransferase-3 gene"Biochem.J.. 373・Pt3. 713-722 (2003)

[Publications] T.Torigoe: "Low pH enhances Sp1 DNA binding activity and interaction with TBP"Nucleic Acids Res.. 31・15. 4523-4530 (2003)

[Publications] H.Izumi: "Cellular pH regulators : potentially promising molecular targets for cancer chemotherapy"Cancer Treat.Rev.. 29・6. 541-549 (2003)

[Publications] M.Tanabe: "Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines"Cancer Res.. 63・24. 8592-8595 (2003)

[Publications] S.Yamamoto: "Expression of uridine diphosphate N-acetyl-α-D-galactosamine : polypeptide N-acetylgalactosaminyl transferase 3 in adenocarcinoma of the pancreas"Pathobiology. 71・1. 12-18 (2004)

[Publications] C.Gu: "Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma : impact on poor prognosis and early recurrence"Br.J.Cancer. 90・2. 436-442 (2004)

[Publications] T.Fukuda: "Characterization of the 5'-untranslated region of YB-1 mRNA and autoregulation of translation by YB-1 protein"Nucleic Acids Res.. 32・2. 611-622 (2004)

河野公俊産業医科大学, 医学部, 教授 (00153479)