{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T18:08:47Z","timestamp":1760897327774},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,10,29]],"date-time":"2002-10-29T00:00:00Z","timestamp":1035849600000},"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":[[2002,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the human <jats:italic>BRCA2<\/jats:italic> breast cancer susceptibility gene are associated with increased risks of breast, ovarian, and other cancers. <jats:italic>BRCA2<\/jats:italic> has been hypothesized to function in processes of DNA damage\/breakage repair, cell proliferation, and apoptosis. These processes continually occur in the thymus during thymocyte development, and <jats:italic>BRCA2<\/jats:italic> mRNA is highly expressed in thymus relative to most other organs. We therefore used the thymus as a model system to study <jats:italic>BRCA2<\/jats:italic> expression and function. Quantitative reverse transcription polymerase chain reaction experiments showed that highly activated immature CD4<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> double\u2010positive human thymocytes that exhibited high levels of proliferation and apoptosis had increased <jats:italic>BRCA2<\/jats:italic> mRNA levels relative to other thymocyte subsets. <jats:italic>BRCA2<\/jats:italic> mRNA levels were upregulated in thymocytes treated with the DNA\u2010damaging agent etoposide. Only modest increases were associated with proliferation in human peripheral lymphocytes in response to concanavalin A (ConA) mitogen. Mice homozygous for a targeted mutation in <jats:italic>Brca2<\/jats:italic> exon 27 (<jats:italic>Brca2<jats:sup>\u039427\/\u039427<\/jats:sup><\/jats:italic>) showed normal thymic architecture but had 18% decreased thymocyte cellularity compared with wild\u2010type mice. Thymocytes from these <jats:italic>Brca2<jats:sup>\u039427\/\u039427<\/jats:sup><\/jats:italic> mice displayed decreased apoptosis in response to etoposide\u2010induced DNA damage compared with wild\u2010type thymocytes. These studies suggest that <jats:italic>BRCA2<\/jats:italic> mRNA levels are modulated during DNA damage and may be important during apoptosis. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10081","type":"journal-article","created":{"date-parts":[[2002,10,31]],"date-time":"2002-10-31T18:21:56Z","timestamp":1036088516000},"page":"103-109","source":"Crossref","is-referenced-by-count":5,"title":["Thymic model for examining <i>BRCA2<\/i> expression and function"],"prefix":"10.1002","volume":"35","author":[{"given":"Kristina G.","family":"Flores","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"McAllister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula K.","family":"Greer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger W.","family":"Wiseman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura P.","family":"Hale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10,29]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201506"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8526"},{"key":"e_1_2_7_4_2","first-page":"1338","article-title":"Thymic lymphomas in mice with a truncating mutation in Brca2","volume":"58","author":"Friedman LS","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-423"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6927"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900623"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.51.31941"},{"key":"e_1_2_7_9_2","first-page":"990","article-title":"Cancer susceptibility of mice with a homozygous deletion in the c\u2010terminal domain of the Brca2 gene","volume":"62","author":"McAllister KA","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138000"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.2144\/99261rv01"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7558"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005824200"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(93)90017-J"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980812)77:4<600::AID-IJC21>3.0.CO;2-8"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80182-3"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80769-2"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073834"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.10081","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.10081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T11:50:56Z","timestamp":1700394656000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.10081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10,29]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["10.1002\/mc.10081"],"URL":"https:\/\/doi.org\/10.1002\/mc.10081","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,10,29]]}}}