{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T21:50:10Z","timestamp":1755035410489},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label \/><jats:p>We have recently identified that phosphorylation at tyrosine (Y)406 is critical for the tumor suppressor functions of the thyroid hormone receptor \u03b21 (TR\u03b2) in a breast cancer line. However, still unclear is whether the critical tumor suppressor role of phosphorylated Y406 of TR\u03b2 is limited to only breast cancer cells or could be extended to other cell types. In the present studies, we addressed this question by stably expressing TR\u03b2, a mutated TR\u03b2 oncogene (PV), or a TR\u03b2 mutated at Y406 (TR\u03b2Y406F) in rat PCCL3 thyroid follicular cells and evaluated their tumor characteristics in athymic mice with elevated thyroid stimulating hormone. PCCL3 cells stably expressing PV (PCCL3\u2010PV), TR\u03b2Y406F (PCCL3\u2010TR\u03b2Y406F), or vector only (PCCL3\u2010Neo) developed tumors with sizes in the rank order of TR\u03b2Y406F&gt;PV\u2009=\u2009Neo, whereas PCCL3 cells expressing TR\u03b2 (PCCL3\u2010TR\u03b2) barely developed tumors. As evidenced by markedly elevated Ki67, cyclin D1, and p\u2010Rb protein abundance, proliferative activity was high in PV and TR\u03b2Y406F tumors, but low in TR\u03b2 tumors. These results indicate that TR\u03b2 acted as a tumor suppressor in PCCL3 cells, whereas TR\u03b2Y406F and PV had lost tumor suppressor activity. Interestingly, TR\u03b2Y406F tumors had very low necrotic areas with decreased TNF\u03b1\u2010NF\u03baB signaling to lower apoptotic activity. In contrast, PV tumors had prominent large necrotic areas, with no apparent changes in TNF\u03b1\u2010NF\u03baB signaling, indicating distinct oncogenic activities of mutant PV and TR\u03b2Y406F. Thus, the present studies uncovered a novel mechanism by which TR\u03b2 could function as a tumor suppressor through modulation of the TNF\u03b1\u2010NF\u03baB signaling. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22511","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T13:21:20Z","timestamp":1464873680000},"page":"489-498","source":"Crossref","is-referenced-by-count":7,"title":["Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor \u03b2"],"prefix":"10.1002","volume":"56","author":[{"given":"Jeong Won","family":"Park","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"Willingham","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheue\u2010yann","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/324641a0"},{"key":"e_1_2_5_3_1","first-page":"282","article-title":"Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers","volume":"44","author":"Leduc F","year":"1989","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870050304"},{"key":"e_1_2_5_5_1","first-page":"3021","article-title":"Deletion of two separate regions on chromosome 3p in breast cancers","volume":"54","author":"Chen LC","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00614-6"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0812"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2009.09.010"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-010-0956-9"},{"key":"e_1_2_5_10_1","first-page":"1939","article-title":"Biallelic inactivation of the thyroid hormone receptor beta1 gene in early stage breast cancer","volume":"62","author":"Li Z","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2198"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.17.7514-7523.2004"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0054"},{"key":"e_1_2_5_14_1","first-page":"302","article-title":"Inhibition of estrogen\u2010dependent tumorigenesis by the thyroid hormone receptor beta in xenograft models","volume":"3","author":"Park JW","year":"2013","journal-title":"Am J Cancer Res"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520469113"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2487"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.180"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.01.007"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3466"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.407"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115542"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2223"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3627"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2628"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4827(02)00027-7"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.09.011"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2065"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2159"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3131"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/105072502320908295"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.1.124-135.2005"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.50"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12262-014-1084-8"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","first-page":"34918","DOI":"10.18632\/oncotarget.9201","article-title":"Quantitative assessment of preoperative serum thyrotropin level and thyroid cancer","volume":"23","author":"Zheng J","year":"2016","journal-title":"Oncotarget"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.5603\/EP.a2015.0059"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599815618388"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2735"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3431"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1997.431"},{"key":"e_1_2_5_40_1","first-page":"1405","article-title":"Decreased expression of the thyroid\u2010stimulating hormone receptor in poorly\u2010differentiated carcinoma of the thyroid","volume":"19","author":"Matsumoto H","year":"2008","journal-title":"Oncol Rep"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-014-0204-z"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1017"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22511","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:12:31Z","timestamp":1709644351000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,14]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1002\/mc.22511"],"URL":"https:\/\/doi.org\/10.1002\/mc.22511","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,14]]}}}