MISC

2003年6月

Formation of an active form of the interleukin-2/15 receptor beta-chain by insertion of the intracisternal A particle in a radiation-induced mouse thymic lymphoma and its role in tumorigenesis

MOLECULAR CARCINOGENESIS
  • H Ukai
  • ,
  • H Ishii-Oba
  • ,
  • M Ukai-Tadenuma
  • ,
  • T Ogiu
  • ,
  • H Tsuji

37
2
開始ページ
110
終了ページ
119
記述言語
英語
掲載種別
DOI
10.1002/mc.10128
出版者・発行元
WILEY-LISS

Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15Rbeta) in cytokine-independent cell lines established from radiation-induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL-2/15Rbeta alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP-IL2/15Rbeta chimeric gene expressed chimeric mRNA in which IAP-coding Gag-Pol mRNA was fused to IL-2/15Rbeta mRNA and coded for Gag-Pol-IL-2/15Rbeta chimeric protein. Forced expression of the Gag-Pol-IL-21/5Rbeta chimeric cDNA in a mouse cytotoxic T-cell line (CTLL-2) converted IL-2-dependent cell growth to IL-2-independent growth, suggesting that the chimeric protein activates some of the IL-2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag-Pol-IL-2/15Rbeta chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c-myc protein. These results suggest that the Gag-Pol-IL-2/15Rbeta is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c-myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL-2-independent autonomous growth potential. (C) 2003 Wiley-Liss, Inc.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1002/mc.10128
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000183315200006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/mc.10128
  • ISSN : 0899-1987
  • identifiers.cinii_nr_id : 9000239248799
  • Web of Science ID : WOS:000183315200006

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