Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity

Frank Un, Christina Qi, Megan Prosser, Norby Wang, Bingsen Zhou, Christian Bronner, Yun Yen

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

Background: Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint, a part of the S-phase checkpoint that responds to DNA damage by inhibiting late origin firing. It also transactivates RR and other genes involved in DNA replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb-associating transactivator for the human topoisomerase IIa gene and responds to DNA damage-induced checkpoint signaling. Materials and Methods: ICBP90 expression was monitored by Western blot. Promoter activity was detected via the luciferase assay and gene silencing via siRNA. Cell death was monitored by the MTT assay. Results: dNTP depletion by HU induced ICBP90, ICBP90 transactivated RR's M2 subunit gene, and ICBP90 induction was necessary for HU-induced M2 accumulation. Blocking the M2 accumulation via anti-ICBP90 siRNA caused greater sensitivity in HU-resistant human cancer. Conclusion: A transcriptional intervention strategy is presented through which HU-resistant cancers may be eradicated without dose escalation.

原文英語
頁(從 - 到)2761-2767
頁數7
期刊Anticancer Research
26
發行號4 B
出版狀態已發佈 - 七月 1 2006
對外發佈Yes

指紋

Hydroxyurea
Ribonucleotide Reductases
Small Interfering RNA
DNA Damage
S Phase Cell Cycle Checkpoints
Deoxyribonucleotides
Genes
Trans-Activators
Gene Silencing
Luciferases
DNA Replication
DNA Repair
Neoplasms
Cell Death
Western Blotting
ribonucleotide reductase M2
Breast Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity. / Un, Frank; Qi, Christina; Prosser, Megan; Wang, Norby; Zhou, Bingsen; Bronner, Christian; Yen, Yun.

於: Anticancer Research, 卷 26, 編號 4 B, 01.07.2006, p. 2761-2767.

研究成果: 雜誌貢獻文章

Un, F, Qi, C, Prosser, M, Wang, N, Zhou, B, Bronner, C & Yen, Y 2006, 'Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity', Anticancer Research, 卷 26, 編號 4 B, 頁 2761-2767.
Un, Frank ; Qi, Christina ; Prosser, Megan ; Wang, Norby ; Zhou, Bingsen ; Bronner, Christian ; Yen, Yun. / Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity. 於: Anticancer Research. 2006 ; 卷 26, 編號 4 B. 頁 2761-2767.
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abstract = "Background: Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint, a part of the S-phase checkpoint that responds to DNA damage by inhibiting late origin firing. It also transactivates RR and other genes involved in DNA replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb-associating transactivator for the human topoisomerase IIa gene and responds to DNA damage-induced checkpoint signaling. Materials and Methods: ICBP90 expression was monitored by Western blot. Promoter activity was detected via the luciferase assay and gene silencing via siRNA. Cell death was monitored by the MTT assay. Results: dNTP depletion by HU induced ICBP90, ICBP90 transactivated RR's M2 subunit gene, and ICBP90 induction was necessary for HU-induced M2 accumulation. Blocking the M2 accumulation via anti-ICBP90 siRNA caused greater sensitivity in HU-resistant human cancer. Conclusion: A transcriptional intervention strategy is presented through which HU-resistant cancers may be eradicated without dose escalation.",
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T1 - Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity

AU - Un, Frank

AU - Qi, Christina

AU - Prosser, Megan

AU - Wang, Norby

AU - Zhou, Bingsen

AU - Bronner, Christian

AU - Yen, Yun

PY - 2006/7/1

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N2 - Background: Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint, a part of the S-phase checkpoint that responds to DNA damage by inhibiting late origin firing. It also transactivates RR and other genes involved in DNA replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb-associating transactivator for the human topoisomerase IIa gene and responds to DNA damage-induced checkpoint signaling. Materials and Methods: ICBP90 expression was monitored by Western blot. Promoter activity was detected via the luciferase assay and gene silencing via siRNA. Cell death was monitored by the MTT assay. Results: dNTP depletion by HU induced ICBP90, ICBP90 transactivated RR's M2 subunit gene, and ICBP90 induction was necessary for HU-induced M2 accumulation. Blocking the M2 accumulation via anti-ICBP90 siRNA caused greater sensitivity in HU-resistant human cancer. Conclusion: A transcriptional intervention strategy is presented through which HU-resistant cancers may be eradicated without dose escalation.

AB - Background: Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint, a part of the S-phase checkpoint that responds to DNA damage by inhibiting late origin firing. It also transactivates RR and other genes involved in DNA replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb-associating transactivator for the human topoisomerase IIa gene and responds to DNA damage-induced checkpoint signaling. Materials and Methods: ICBP90 expression was monitored by Western blot. Promoter activity was detected via the luciferase assay and gene silencing via siRNA. Cell death was monitored by the MTT assay. Results: dNTP depletion by HU induced ICBP90, ICBP90 transactivated RR's M2 subunit gene, and ICBP90 induction was necessary for HU-induced M2 accumulation. Blocking the M2 accumulation via anti-ICBP90 siRNA caused greater sensitivity in HU-resistant human cancer. Conclusion: A transcriptional intervention strategy is presented through which HU-resistant cancers may be eradicated without dose escalation.

KW - Checkpoint

KW - Hydroxyurea

KW - ICBP90

KW - Lytic path

KW - Ribonucleotide reductase

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