MISC

2006年10月

Overexpression of PIAS3 suppresses cell growth and restores the drug sensitivity of human lung cancer cells in association with PI3-K/Akt inactivation

NEOPLASIA
  • Yoshitaka Ogata
  • Tadashi Osaki
  • Tetsuji Naka
  • Kota Iwahori
  • Mitsugi Furukawa
  • Izumi Nagatomo
  • Takashi Kijima
  • Toru Kumagai
  • Mitsuhiro Yoshida
  • Isao Tachibana
  • Ichiro Kawase
  • 全て表示

8
10
開始ページ
817
終了ページ
825
記述言語
英語
掲載種別
DOI
10.1593/neo.06409
出版者・発行元
NEOPLASIA PRESS

Constitutively activated signal transducers and activators of transcription ( STAT) are reported to cause uncontrolled transmission of growth signals. In this study, we analyzed the roles of an inhibitor of STAT, protein inhibitor of activated STAT ( PIAS) 3, in the development of lung cancer. Treatment with an inhibitor of phosphatidylinositol 3-kinase, LY294002, retarded the growth of human lung cancer cells and rendered them more sensitive to chemotherapeutic agents. However, the inhibition of JAK/STAT by AG490 significantly suppressed cell growth but did not increase drug sensitivity at all. Overexpression of PIAS3 not only significantly inhibited cell growth but also rendered cancer cells up to 12.0-fold more sensitive to the above drugs, which was associated with the suppression of Akt phosphorylation. Inhibition of PIAS3 with small interfering RNA, nevertheless, led cancer cells to accelerate cell proliferation, deteriorate chemosensitivity, and augment Akt phosphorylation. Although the overexpression of suppressors of cytokine signaling 3 in cancer cells also inhibited cell growth and STAT3 phosphorylation, it neither increased sensitivity to chemotherapeutic drugs nor affected the phosphorylation of Akt. These results indicate that PIAS3 may be an attractive candidate for targeting the JAK/STAT and PI3-K/Akt signaling pathways in cancer treatment.

リンク情報
DOI
https://doi.org/10.1593/neo.06409
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000241365400004&DestApp=WOS_CPL
ID情報
  • DOI : 10.1593/neo.06409
  • ISSN : 1522-8002
  • Web of Science ID : WOS:000241365400004

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