{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:09:42Z","timestamp":1781104182975,"version":"3.54.1"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,7,22]]},"abstract":"\n A key issue in cancer biology is whether genetic lesions involved in tumor\n initiation or progression are required for tumor maintenance. This question\n can be addressed with mouse models that conditionally express oncogenic\n transgenes, i.e., under the control of tetracycline (tet)-dependent\n transcriptional regulators. We have developed a system for studying tumor\n maintenance by using avian retroviral [i.e., replication-competent avian\n leukosis virus long terminal repeat with splice acceptor (RCAS)] vectors to\n deliver the reverse tet transcriptional transactivator (rtTA) gene to somatic\n mammalian cells. rtTA can regulate any transgene in which the protein coding\n sequence is preceded by a tet-operator (tet-o); RCAS viruses infect only cells\n engineered to express ectopically the avian retroviral receptor, TVA. One\n vector, RCAS-\n rtTA-IRES-GFP<\/jats:italic>\n , also encodes GFP to identify infected\n cells. Infection of cells from \u03b2-actin TVA transgenic mice with this\n vector permits efficient regulation of tet-responsive transgenes. Sarcomas\n arise when p53-deficient murine embryonic fibroblasts carrying \u03b2-actin\n TVA and tet-o-\n \n K-ras4b\n G12D<\/jats:sup>\n <\/jats:italic>\n transgenes are infected with\n RCAS-\n rtTA-IRES-GFP<\/jats:italic>\n and introduced into nude mice treated with the tet\n analog, doxycycline (dox); when dox is withdrawn,\n \n K-ras4b\n G12D<\/jats:sup>\n <\/jats:italic>\n levels fall, cells undergo apoptosis, and\n tumors regress. Regression can be prevented by means of a genetic\n complementation assay in which tumors are superinfected before dox withdrawal\n with other RCAS viruses, such as those carrying an active allele of\n K-ras<\/jats:italic>\n . Many TVA and tet-regulated transgenic mice have been\n generated; thus, this method for somatic cell-specific and temporally\n controlled gene expression may have broad applications for the study of\n oncogenesis and tumor maintenance, as well as other cell functions and\n development.\n <\/jats:p>","DOI":"10.1073\/pnas.1133333100","type":"journal-article","created":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T15:39:06Z","timestamp":1058888346000},"page":"8764-8769","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance"],"prefix":"10.1073","volume":"100","author":[{"given":"William","family":"Pao","sequence":"first","affiliation":[{"name":"Departments of Medicine and\r Pathology, and\r Program in Cell Biology, Memorial\r Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and\r National Cancer Institute, Division of Basic\r Sciences, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Klimstra","sequence":"additional","affiliation":[{"name":"Departments of Medicine and\r Pathology, and\r Program in Cell Biology, Memorial\r Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and\r National Cancer Institute, Division of Basic\r Sciences, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen H.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Departments of Medicine and\r Pathology, and\r Program in Cell Biology, Memorial\r Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and\r National Cancer Institute, Division of Basic\r Sciences, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold E.","family":"Varmus","sequence":"additional","affiliation":[{"name":"Departments of Medicine and\r Pathology, and\r Program in Cell Biology, Memorial\r Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and\r National Cancer Institute, Division of Basic\r Sciences, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,7,11]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(93)90209-Z"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1070"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073096"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.10933"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203087"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-002-4003-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.23.3675"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(01)00002-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.10.4931"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.947701"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00002-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9290"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9291"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.3.493"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90132-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.11241"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.23.3644"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3065"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0065com"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6705"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.21.10202-10206.2000"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/217370a0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/22788"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.130192197"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1133333100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T21:28:47Z","timestamp":1650922127000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1133333100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7,11]]},"references-count":24,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2003,7,22]]}},"alternative-id":["10.1073\/pnas.1133333100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1133333100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7,11]]},"assertion":[{"value":"2003-07-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}