Identification of proteasomal catalytic subunit <i><scp>PSMA</scp>6</i> as a therapeutic target for lung cancer

DOI Web Site Web Site PubMed 被引用文献4件 参考文献39件 オープンアクセス
  • Tomohiko Kakumu
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Mitsuo Sato
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Daiki Goto
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Toshio Kato
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Naoyuki Yogo
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Tetsunari Hase
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Masahiro Morise
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Takayuki Fukui
    Department of Thoracic Surgery Nagoya University Graduate School of Medicine Nagoya Japan
  • Kohei Yokoi
    Department of Thoracic Surgery Nagoya University Graduate School of Medicine Nagoya Japan
  • Yoshitaka Sekido
    Department of Cancer Genetics Nagoya University Graduate School of Medicine Nagoya Japan
  • Luc Girard
    Hamon Center for Therapeutic Oncology Research and the Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center at Dallas Dallas Texas USA
  • John D. Minna
    Hamon Center for Therapeutic Oncology Research and the Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center at Dallas Dallas Texas USA
  • Lauren A. Byers
    Department of Thoracic/Head & Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA
  • John V. Heymach
    Department of Thoracic/Head & Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA
  • Kevin R. Coombes
    Department of Biomedical Informatics Ohio State University Columbus Ohio USA
  • Masashi Kondo
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan
  • Yoshinori Hasegawa
    Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan

この論文をさがす

説明

<jats:p>To identify potential therapeutic targets for lung cancer, we performed semi‐genome‐wide sh<jats:styled-content style="fixed-case">RNA</jats:styled-content> screening combined with the utilization of genome‐wide expression and copy number data. sh<jats:styled-content style="fixed-case">RNA</jats:styled-content> screening targeting 5043 genes in <jats:styled-content style="fixed-case">NCI</jats:styled-content>‐H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, <jats:styled-content style="fixed-case">RNA</jats:styled-content> polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array <jats:styled-content style="fixed-case">CGH</jats:styled-content> data showed that <jats:italic><jats:styled-content style="fixed-case">PSMA</jats:styled-content>6</jats:italic>, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of <jats:italic><jats:styled-content style="fixed-case">PSMA</jats:styled-content>6</jats:italic> in lung cancer. Silencing of <jats:italic><jats:styled-content style="fixed-case">PSMA</jats:styled-content>6</jats:italic> induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that <jats:italic><jats:styled-content style="fixed-case">PSMA</jats:styled-content>6</jats:italic> serves as an attractive target with a high therapeutic index for lung cancer.</jats:p>

収録刊行物

被引用文献 (4)*注記

もっと見る

参考文献 (39)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ