{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:53:28Z","timestamp":1776495208562,"version":"3.51.2"},"reference-count":47,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":3394,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cell"],"published-print":{"date-parts":[[2004,4]]},"DOI":"10.1016\/s1535-6108(04)00085-6","type":"journal-article","created":{"date-parts":[[2004,4,21]],"date-time":"2004-04-21T06:28:17Z","timestamp":1082528897000},"page":"375-387","source":"Crossref","is-referenced-by-count":692,"title":["Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects"],"prefix":"10.1016","volume":"5","author":[{"given":"David A","family":"Tuveson","sequence":"first","affiliation":[]},{"given":"Alice T","family":"Shaw","sequence":"additional","affiliation":[]},{"given":"Nicholas A","family":"Willis","sequence":"additional","affiliation":[]},{"given":"Daniel P","family":"Silver","sequence":"additional","affiliation":[]},{"given":"Erica L","family":"Jackson","sequence":"additional","affiliation":[]},{"given":"Sandy","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Kim L","family":"Mercer","sequence":"additional","affiliation":[]},{"given":"Rebecca","family":"Grochow","sequence":"additional","affiliation":[]},{"given":"Hanno","family":"Hock","sequence":"additional","affiliation":[]},{"given":"Denise","family":"Crowley","sequence":"additional","affiliation":[]},{"given":"Sunil R","family":"Hingorani","sequence":"additional","affiliation":[]},{"given":"Tal","family":"Zaks","sequence":"additional","affiliation":[]},{"given":"Catrina","family":"King","sequence":"additional","affiliation":[]},{"given":"Michael A","family":"Jacobetz","sequence":"additional","affiliation":[]},{"given":"Lifu","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Roderick T","family":"Bronson","sequence":"additional","affiliation":[]},{"given":"Stuart H","family":"Orkin","sequence":"additional","affiliation":[]},{"given":"Ronald A","family":"DePinho","sequence":"additional","affiliation":[]},{"given":"Tyler","family":"Jacks","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S1535-6108(04)00085-6_BIB1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0165-1110(88)90004-8","article-title":"The ras gene family and human carcinogenesis","volume":"195","author":"Bos","year":"1988","journal-title":"Mutat. Res."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB2","first-page":"4682","article-title":"ras oncogenes in human cancer","volume":"49","author":"Bos","year":"1989","journal-title":"Cancer Res."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1073\/pnas.0307203101","article-title":"Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder","volume":"101","author":"Braun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB4","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1172\/JCI20476","article-title":"Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease","volume":"113","author":"Chan","year":"2004","journal-title":"J. Clin. Invest."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB5","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1101\/gad.12.15.2434","article-title":"E1A signaling to p53 involves the p19(ARF) tumor suppressor","volume":"12","author":"de Stanchina","year":"1998","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB6","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1101\/gad.828901","article-title":"Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells","volume":"15","author":"Elenbaas","year":"2001","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB8","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/j.1460-2075.1985.tb03760.x","article-title":"Structure and expression of amplified cKi-ras gene sequences in Y1 mouse adrenal tumor cells","volume":"4","author":"George","year":"1985","journal-title":"EMBO J."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB9","doi-asserted-by":"crossref","first-page":"27473","DOI":"10.1016\/S0021-9258(19)61532-2","article-title":"Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases","volume":"275","author":"Groth","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1535-6108(03)00191-0","article-title":"Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context","volume":"4","author":"Guerra","year":"2003","journal-title":"Cancer Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB11","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1101\/gad.5.12b.2375","article-title":"p53 alteration is a common event in the spontaneous immortalization of primary BALB\/c murine embryo fibroblasts","volume":"5","author":"Harvey","year":"1991","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB13","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1101\/gad.943001","article-title":"Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras","volume":"15","author":"Jackson","year":"2001","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB14","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/35074129","article-title":"Somatic activation of the K-ras oncogene causes early onset lung cancer in mice","volume":"410","author":"Johnson","year":"2001","journal-title":"Nature"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB15","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0092-8674(00)80452-3","article-title":"Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF","volume":"91","author":"Kamijo","year":"1997","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB16","doi-asserted-by":"crossref","first-page":"8292","DOI":"10.1073\/pnas.95.14.8292","article-title":"Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2","volume":"95","author":"Kamijo","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB17","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/304596a0","article-title":"Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes","volume":"304","author":"Land","year":"1983","journal-title":"Nature"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB18","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1101\/gad.12.19.3008","article-title":"Premature senescence involving p53 and p16 is activated in response to constitutive MEK\/MAPK mitogenic signaling","volume":"12","author":"Lin","year":"1998","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB19","doi-asserted-by":"crossref","first-page":"9209","DOI":"10.1073\/pnas.161269798","article-title":"Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells","volume":"98","author":"Loonstra","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0959-437X(02)00013-8","article-title":"Tumor suppression by Ink4a-Arf","volume":"13","author":"Lowe","year":"2003","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/014850199262733","article-title":"Expression and phosphorylation of mitogen-activated protein kinases during spermatogenesis and epididymal sperm maturation in mice","volume":"43","author":"Lu","year":"1999","journal-title":"Arch. Androl."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB22","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrc1097","article-title":"RAS oncogenes","volume":"3","author":"Malumbres","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB23","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1128\/MCB.14.3.2066","article-title":"D-type cyclin-dependent kinase activity in mammalian cells","volume":"14","author":"Matsushime","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB24","first-page":"2140","article-title":"p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma","volume":"57","author":"Moskaluk","year":"1997","journal-title":"Cancer Res."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB25","doi-asserted-by":"crossref","first-page":"14602","DOI":"10.1073\/pnas.94.26.14602","article-title":"Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells","volume":"94","author":"O'Gorman","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB26","doi-asserted-by":"crossref","first-page":"4974","DOI":"10.1038\/sj.onc.1202880","article-title":"Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras","volume":"18","author":"Pantoja","year":"1999","journal-title":"Oncogene"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB27","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0092-8674(00)81400-2","article-title":"The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53","volume":"92","author":"Pomerantz","year":"1998","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB28","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/304602a0","article-title":"Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture","volume":"304","author":"Ruley","year":"1983","journal-title":"Nature"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB29","doi-asserted-by":"crossref","first-page":"38071","DOI":"10.1074\/jbc.274.53.38071","article-title":"Inducible gene knockouts in the small intestinal and colonic epithelium","volume":"274","author":"Saam","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB30","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1101\/gad.843200","article-title":"Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization","volume":"14","author":"Sage","year":"2000","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB31","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1093\/nar\/23.24.5080","article-title":"A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells","volume":"23","author":"Schwenk","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB32","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1073\/pnas.76.10.5355","article-title":"Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses","volume":"76","author":"Scolnick","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0092-8674(00)81079-X","article-title":"Role of the INK4a locus in tumor suppression and cell mortality","volume":"85","author":"Serrano","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB34","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0092-8674(00)81902-9","article-title":"Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a","volume":"88","author":"Serrano","year":"1997","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/35092592","article-title":"Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis","volume":"413","author":"Sharpless","year":"2001","journal-title":"Nature"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB36","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/sj.leu.2402577","article-title":"Chronic myelogenous leukemia","volume":"16","author":"Shet","year":"2002","journal-title":"Leukemia"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1097-2765(01)00295-7","article-title":"Self-excising retroviral vectors encoding the Cre recombinase overcome Cre-mediated cellular toxicity","volume":"8","author":"Silver","year":"2001","journal-title":"Mol. Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB38","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/215171a0","article-title":"Density dependent inhibition of cell growth in culture","volume":"215","author":"Stoker","year":"1967","journal-title":"Nature"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/0092-8674(94)90132-5","article-title":"Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1","volume":"77","author":"Tanaka","year":"1994","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB40","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/S0960-9822(02)70785-9","article-title":"Cell cycle-dependent activation of Ras","volume":"6","author":"Taylor","year":"1996","journal-title":"Curr. Biol."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB41","first-page":"153","article-title":"Biochemical mechanisms of oncogene activity","volume":"5","author":"Varmus","year":"1986","journal-title":"Cancer Surv."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB42","doi-asserted-by":"crossref","first-page":"8551","DOI":"10.1073\/pnas.96.15.8551","article-title":"The magical touch","volume":"96","author":"Vasioukhin","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB43","doi-asserted-by":"crossref","first-page":"19925","DOI":"10.1074\/jbc.273.32.19925","article-title":"Increasing complexity of the Ras signaling pathway","volume":"273","author":"Vojtek","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB44","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1093\/nar\/25.21.4323","article-title":"Cre-mediated gene deletion in the mammary gland","volume":"25","author":"Wagner","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB45","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0092-8674(00)81401-4","article-title":"ARF promotes MDM2 degradation and stabilizes p53","volume":"92","author":"Zhang","year":"1998","journal-title":"Cell"},{"key":"10.1016\/S1535-6108(04)00085-6_BIB46","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1101\/gad.12.19.2997","article-title":"Senescence of human fibroblasts induced by oncogenic Raf","volume":"12","author":"Zhu","year":"1998","journal-title":"Genes Dev."},{"key":"10.1016\/S1535-6108(04)00085-6_BIB47","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1101\/gad.12.15.2424","article-title":"Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization","volume":"12","author":"Zindy","year":"1998","journal-title":"Genes Dev."}],"container-title":["Cancer Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535610804000856?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535610804000856?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T14:11:52Z","timestamp":1623852712000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1535610804000856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["S1535610804000856"],"URL":"https:\/\/doi.org\/10.1016\/s1535-6108(04)00085-6","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1004496.211477","asserted-by":"object"}]},"ISSN":["1535-6108"],"issn-type":[{"value":"1535-6108","type":"print"}],"subject":[],"published":{"date-parts":[[2004,4]]}}}