{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:52:14Z","timestamp":1790866334714,"version":"4.1.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,12,2]]},"abstract":"<jats:p>\n                    Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Wnt signaling is key. Here, using cre-lox technology, we deleted the\n                    <jats:italic>Apc<\/jats:italic>\n                    gene in the adult mouse liver and observed a rapid increase in nuclear \u03b2-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors \u03b2-catenin and c-Myc. \u03b2-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Wnt pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Wnt targets being \u03b2-catenin-dependent but c-Myc-independent in the liver.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0805778105","type":"journal-article","created":{"date-parts":[[2008,11,24]],"date-time":"2008-11-24T21:56:49Z","timestamp":1227563809000},"page":"18919-18923","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":64,"title":["B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver"],"prefix":"10.1073","volume":"105","author":[{"given":"Karen R.","family":"Reed","sequence":"first","affiliation":[{"name":"School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Athineos","sequence":"additional","affiliation":[{"name":"Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie S.","family":"Meniel","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Ridgway","sequence":"additional","affiliation":[{"name":"Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00e9 D.","family":"Burke","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, University of Bath, Bath BA2 7AY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Muncan","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Leiden, The Netherlands, 2333ZA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Clarke","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen J.","family":"Sansom","sequence":"additional","affiliation":[{"name":"Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,12,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.2741\/1933"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209824"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1787"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205591"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/73448"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404761101"},{"key":"e_1_3_3_7_2","first-page":"1971","article-title":"Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin","volume":"62","author":"Harada N","year":"2002","unstructured":"N Harada, et al., Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res 62, 1971\u20131977 (2002).","journal-title":"Cancer Res"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2123"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.03.015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.287404"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05674"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.03.020"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.120"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65297-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5382.1509"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404875101"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409260102"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2006.07.014"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01015-2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03626"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507582200"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.042"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4242"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1649"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1455706"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00821-06"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.9.e36"}],"updated-by":[{"DOI":"10.1073\/pnas.1502294112","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,2,20]],"date-time":"2015-02-20T00:00:00Z","timestamp":1424390400000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0805778105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:41:08Z","timestamp":1649785268000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0805778105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,2]]},"references-count":29,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2008,12,2]]}},"alternative-id":["10.1073\/pnas.0805778105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0805778105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,2]]},"assertion":[{"value":"2008-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-12-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}