{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:21:47Z","timestamp":1792272107366,"version":"4.4.0"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,3,27]]},"abstract":"<jats:p>\n                    Identifying the cells of origin of lung cancer may lead to new therapeutic strategies. Previous work has focused upon the putative bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we use two \u201cknock-in\u201d Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10\n                    <jats:sup>+<\/jats:sup>\n                    epithelial cells and Sftpc\n                    <jats:sup>+<\/jats:sup>\n                    type II alveolar cells of the adult mouse lung. Analysis of these mice identifies type II cells, Clara cells in the terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin for K-Ras\u2013induced lung hyperplasia. However, only type II cells appear to progress to adenocarcinoma.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1112499109","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T01:00:12Z","timestamp":1331600412000},"page":"4910-4915","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":274,"title":["Evidence for type II cells as cells of origin of K-Ras\u2013induced distal lung adenocarcinoma"],"prefix":"10.1073","volume":"109","author":[{"given":"Xia","family":"Xu","sequence":"first","affiliation":[{"name":"Departments of aSurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Rock","sequence":"additional","affiliation":[{"name":"Cell Biology, Duke University, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Tsingua University, Beijing 100084, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Futtner","sequence":"additional","affiliation":[{"name":"Departments of aSurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Schwab","sequence":"additional","affiliation":[{"name":"Departments of aSurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Guinney","sequence":"additional","affiliation":[{"name":"Sage Bionetworks, Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid L. M.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Cell Biology, Duke University, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Onaitis","sequence":"additional","affiliation":[{"name":"Departments of aSurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,3,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07423"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/142.6_Pt_2.S27"},{"key":"e_1_3_3_3_2","first-page":"4682","article-title":"ras oncogenes in human cancer: A review","volume":"49","author":"Bos JL","year":"1989","unstructured":"JL Bos, ras oncogenes in human cancer: A review. Cancer Res 49, 4682\u20134689 (1989).","journal-title":"Cancer Res"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2005.70.037"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2010.05.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.032"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.943001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1790"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780090710"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204837"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2037"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002220"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.157"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909207107"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900668106"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117988108"},{"key":"e_1_3_3_18_2","first-page":"6997","article-title":"BRAF and RAS mutations in human lung cancer and melanoma","volume":"62","author":"Brose MS","year":"2002","unstructured":"MS Brose, et al., BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62, 6997\u20137000 (2002).","journal-title":"Cancer Res"},{"key":"e_1_3_3_19_2","first-page":"1037","article-title":"Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products","volume":"5","author":"Suzuki Y","year":"1990","unstructured":"Y Suzuki, M Orita, M Shiraishi, K Hayashi, T Sekiya, Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene 5, 1037\u20131043 (1990).","journal-title":"Oncogene"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-984PP"},{"key":"e_1_3_3_21_2","first-page":"3164","article-title":"Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the A\/J mouse","volume":"52","author":"Belinsky SA","year":"1992","unstructured":"SA Belinsky, TR Devereux, JF Foley, RR Maronpot, MW Anderson, Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the A\/J mouse. Cancer Res 52, 3164\u20133173 (1992).","journal-title":"Cancer Res"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199704)181:4<401::AID-PATH799>3.0.CO;2-Y"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1112499109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:58:09Z","timestamp":1649797089000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1112499109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,12]]},"references-count":22,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2012,3,27]]}},"alternative-id":["10.1073\/pnas.1112499109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1112499109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,12]]},"assertion":[{"value":"2012-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}