{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:34:13Z","timestamp":1790627653236,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,5,19]],"date-time":"2003-05-19T00:00:00Z","timestamp":1053302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin\u20102 receptor (IL\u20102R) induces tumorigenic transformation, constitutively active IL\u20102R in tumors has not been reported. We searched for genomic alteration of the IL\u20102\/15R \u03b2\u2010subunit gene (<jats:italic>IL\u20102<\/jats:italic>\/<jats:italic>15R\u03b2<\/jats:italic>) in cytokine\u2010independent cell lines established from radiation\u2010induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the <jats:italic>IL\u20102<\/jats:italic>\/<jats:italic>15R\u03b2<\/jats:italic> alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The <jats:italic>IAP\u2010IL2<\/jats:italic>\/<jats:italic>15R\u03b2<\/jats:italic> chimeric gene expressed chimeric mRNA in which IAP\u2010coding <jats:italic>Gag\u2010Pol<\/jats:italic> mRNA was fused to <jats:italic>IL\u20102<\/jats:italic>\/<jats:italic>15R\u03b2<\/jats:italic> mRNA and coded for Gag\u2010Pol\u2010IL\u20102\/15R\u03b2 chimeric protein. Forced expression of the <jats:italic>Gag\u2010Pol\u2010IL\u20102<\/jats:italic>\/<jats:italic>15R\u03b2<\/jats:italic> chimeric cDNA in a mouse cytotoxic T\u2010cell line (CTLL\u20102) converted IL\u20102\u2010dependent cell growth to IL\u20102\u2010independent growth, suggesting that the chimeric protein activates some of the IL\u20102 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag\u2010Pol\u2010IL\u20102\/15R\u03b2 chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c\u2010myc protein. These results suggest that the Gag\u2010Pol\u2010IL\u20102\/15R\u03b2 is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c\u2010<jats:italic>myc<\/jats:italic>. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL\u20102\u2010independent autonomous growth potential. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10128","type":"journal-article","created":{"date-parts":[[2003,5,21]],"date-time":"2003-05-21T10:02:10Z","timestamp":1053511330000},"page":"110-119","source":"Crossref","is-referenced-by-count":14,"title":["Formation of an active form of the interleukin\u20102\/15 receptor \u03b2\u2010chain by insertion of the intracisternal A particle in a radiation\u2010induced mouse thymic lymphoma and its role in tumorigenesis"],"prefix":"10.1002","volume":"37","author":[{"given":"Hideki","family":"Ukai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Ishii\u2010Oba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Ukai\u2010Tadenuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Ogiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,5,19]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716517"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90098-T"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.1.7821759"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266076"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128231"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06576.x"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8178155"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266077"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266078"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.1.115"},{"key":"e_1_2_7_12_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1182\/blood.V68.3.779.779","article-title":"Autocrine growth of interleukin 2\u2010producing leukemic cells in a patient with adult T cell leukemia","volume":"68","author":"Arima N","year":"1986","journal-title":"Blood"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.154.5.1403"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90437-5"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02563.x"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.1.13"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141224998"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230523"},{"key":"e_1_2_7_19_2","first-page":"1327","article-title":"Thymic lymphomas in interleukin 9 transgenic mice","volume":"9","author":"Renauld JC","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.2.305"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910600606"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90533-I"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.17.5797-5805.2001"},{"key":"e_1_2_7_24_2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4049\/jimmunol.157.2.643","article-title":"The effect of IL\u20102 treatment on transcriptional attenuation in proto\u2010oncogenes pim\u20101 and c\u2010myb in human thymic blast cells","volume":"157","author":"Rohwer F","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_7_25_2","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1182\/blood.V87.7.2641.bloodjournal8772641","article-title":"Extracellular truncations of h beta c, the common signaling subunit for interleukin\u20103 (IL\u20103), granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF), and IL\u20105, lead to ligand\u2010independent activation","volume":"87","author":"D'Andrea RJ","year":"1996","journal-title":"Blood"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.2.355"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.5.1806"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205262"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02341614"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10285"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60223-7"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.3.1093"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1984.tb02235.x"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.11.5562"},{"key":"e_1_2_7_35_2","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1128\/JVI.73.6.5166-5171.1999","article-title":"Intracisternal type A particle\u2013mediated activation of the Notch4\/int3 gene in a mouse mammary tumor: Generation of truncated Notch4\/int3 mRNAs by retroviral splicing events","volume":"73","author":"Lee JS","year":"1999","journal-title":"J Virol"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.10.3095"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(02)00107-4"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/10.2.459"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240941"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077213"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/369330a0"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1309"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02258360"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.1.19"},{"key":"e_1_2_7_45_2","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1182\/blood.V90.9.3720","article-title":"Disruption of the multiple tumor suppressor gene MTS1\/p16(INK4a)\/CDKN2 by illegitimate V(D)J recombinase activity in T\u2010cell acute lymphoblastic leukemias","volume":"90","author":"Cayuela JM","year":"1997","journal-title":"Blood"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07535.x"},{"key":"e_1_2_7_47_2","first-page":"27","article-title":"Are interleukin\u20102 and interleukin\u201015 tumor promoting factors for human non\u2010hematopoietic cells?","volume":"7","author":"Azzarone B","year":"1996","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad928101"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.143"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0501-29"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.10128","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.10128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T13:57:36Z","timestamp":1695909456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.10128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5,19]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1002\/mc.10128"],"URL":"https:\/\/doi.org\/10.1002\/mc.10128","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5,19]]}}}