{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:50:02Z","timestamp":1784155802638,"version":"3.55.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,10,18]]},"abstract":"<jats:p>The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and\/or apoptosis, a phenomenon known as oncogene addiction. However, after prolonged inactivation of MYC in a conditional transgenic mouse model of E\u03bc-tTA\/tetO-MYC T-cell acute lymphoblastic leukemia, some of the tumors recur, recapitulating what is frequently observed in human tumors in response to targeted therapies. Here we report that these recurring lymphomas express either transgenic or endogenous Myc, albeit in many cases at levels below those in the original tumor, suggesting that tumors continue to be addicted to MYC. Many of the recurring lymphomas (76%) harbored mutations in the tetracycline transactivator, resulting in expression of the MYC transgene even in the presence of doxycycline. Some of the remaining recurring tumors expressed high levels of endogenous Myc, which was associated with a genomic rearrangement of the endogenous Myc locus or activation of Notch1. By gene expression profiling, we confirmed that the primary and recurring tumors have highly similar transcriptomes. Importantly, shRNA-mediated suppression of the high levels of MYC in recurring tumors elicited both suppression of proliferation and increased apoptosis, confirming that these tumors remain oncogene addicted. These results suggest that tumors induced by MYC remain addicted to overexpression of this oncogene.<\/jats:p>","DOI":"10.1073\/pnas.1107303108","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T00:09:41Z","timestamp":1317686981000},"page":"17432-17437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction"],"prefix":"10.1073","volume":"108","author":[{"given":"Peter S.","family":"Choi","sequence":"first","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Riggelen","sequence":"additional","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Gentles","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Bachireddy","sequence":"additional","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavya","family":"Rakhra","sequence":"additional","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey J.","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia K.","family":"Plevritis","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean W.","family":"Felsher","sequence":"additional","affiliation":[{"name":"Division of Oncology, Departments of Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,10,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1101\/gad.1712408","article-title":"Myc's broad reach","volume":"22","author":"Eilers M","year":"2008","unstructured":"M Eilers, RN Eisenman, Myc's broad reach. Genes Dev 22, 2755\u20132766 (2008).","journal-title":"Genes Dev"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MCB.19.1.1","article-title":"c-Myc target genes involved in cell growth, apoptosis, and metabolism","volume":"19","author":"Dang CV","year":"1999","unstructured":"CV Dang, c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19, 1\u201311 (1999).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.semcancer.2006.07.014","article-title":"The c-Myc target gene network","volume":"16","author":"Dang CV","year":"2006","unstructured":"CV Dang, et al., The c-Myc target gene network. Semin Cancer Biol 16, 253\u2013264 (2006).","journal-title":"Semin Cancer Biol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1146\/annurev.cellbio.16.1.653","article-title":"The Myc\/Max\/Mad network and the transcriptional control of cell behavior","volume":"16","author":"Grandori C","year":"2000","unstructured":"C Grandori, SM Cowley, LP James, RN Eisenman, The Myc\/Max\/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16, 653\u2013699 (2000).","journal-title":"Annu Rev Cell Dev Biol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0003-9861(03)00294-7","article-title":"The many faces of c-MYC","volume":"416","author":"Pelengaris S","year":"2003","unstructured":"S Pelengaris, M Khan, The many faces of c-MYC. Arch Biochem Biophys 416, 129\u2013136 (2003).","journal-title":"Arch Biochem Biophys"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nrc1070","article-title":"Cancer revoked: Oncogenes as therapeutic targets","volume":"3","author":"Felsher DW","year":"2003","unstructured":"DW Felsher, Cancer revoked: Oncogenes as therapeutic targets. Nat Rev Cancer 3, 375\u2013380 (2003).","journal-title":"Nat Rev Cancer"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ccr.2004.10.013","article-title":"Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation","volume":"6","author":"Boxer RB","year":"2004","unstructured":"RB Boxer, JW Jang, L Sintasath, LA Chodosh, Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6, 577\u2013586 (2004).","journal-title":"Cancer Cell"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/84691","article-title":"c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations","volume":"7","author":"D'Cruz CM","year":"2001","unstructured":"CM D'Cruz, et al., c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7, 235\u2013239 (2001).","journal-title":"Nat Med"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1097-2765(00)80367-6","article-title":"Reversible tumorigenesis by MYC in hematopoietic lineages","volume":"4","author":"Felsher DW","year":"1999","unstructured":"DW Felsher, JM Bishop, Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4, 199\u2013207 (1999).","journal-title":"Mol Cell"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1071489","article-title":"Sustained loss of a neoplastic phenotype by brief inactivation of MYC","volume":"297","author":"Jain M","year":"2002","unstructured":"M Jain, et al., Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science (New York, N.Y.) 297, 102\u2013104 (2002).","journal-title":"Science (New York, N.Y.)"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0092-8674(02)00738-9","article-title":"Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression","volume":"109","author":"Pelengaris S","year":"2002","unstructured":"S Pelengaris, M Khan, GI Evan, Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109, 321\u2013334 (2002).","journal-title":"Cell"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1097-2765(00)80350-0","article-title":"Reversible activation of c-Myc in skin: Induction of a complex neoplastic phenotype by a single oncogenic lesion","volume":"3","author":"Pelengaris S","year":"1999","unstructured":"S Pelengaris, T Littlewood, M Khan, G Elia, G Evan, Reversible activation of c-Myc in skin: Induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol Cell 3, 565\u2013577 (1999).","journal-title":"Mol Cell"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nature03043","article-title":"MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer","volume":"431","author":"Shachaf CM","year":"2004","unstructured":"CM Shachaf, et al., MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431, 1112\u20131117 (2004).","journal-title":"Nature"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"e2125","DOI":"10.1371\/journal.pone.0002125","article-title":"Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas","volume":"3","author":"Tran PT","year":"2008","unstructured":"PT Tran, et al., Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS ONE 3, e2125 (2008).","journal-title":"PLoS ONE"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1101\/gad.585710","article-title":"The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance","volume":"24","author":"van Riggelen J","year":"2010","unstructured":"J van Riggelen, et al., The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance. Genes Dev 24, 1281\u20131294 (2010).","journal-title":"Genes Dev"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"13028","DOI":"10.1073\/pnas.0701953104","article-title":"Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation","volume":"104","author":"Wu CH","year":"2007","unstructured":"CH Wu, et al., Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci USA 104, 13028\u201313033 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1158\/0008-5472.CAN-07-5832","article-title":"Oncogene addiction versus oncogene amnesia: Perhaps more than just a bad habit?","volume":"68","author":"Felsher DW","year":"2008","unstructured":"DW Felsher, Oncogene addiction versus oncogene amnesia: Perhaps more than just a bad habit? Cancer Res 68, 3081\u20133086, discussion 3086. (2008).","journal-title":"Cancer Res"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.4161\/cc.8.17.9336","article-title":"Oncogenic K-ras \u201caddiction\u201d and synthetic lethality","volume":"8","author":"Singh A","year":"2009","unstructured":"A Singh, J Settleman, Oncogenic K-ras \u201caddiction\u201d and synthetic lethality. Cell Cycle 8, 2676\u20132677 (2009).","journal-title":"Cell Cycle"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1126\/science.1073096","article-title":"Cancer. Addiction to oncogenes\u2014the Achilles heal of cancer","volume":"297","author":"Weinstein IB","year":"2002","unstructured":"IB Weinstein, Cancer. Addiction to oncogenes\u2014the Achilles heal of cancer. Science 297, 63\u201364 (2002).","journal-title":"Science"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1056\/NEJM199904293401706","article-title":"Chronic myeloid leukemia","volume":"340","author":"Sawyers CL","year":"1999","unstructured":"CL Sawyers, Chronic myeloid leukemia. N Engl J Med 340, 1330\u20131340 (1999).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.bcp.2010.05.014","article-title":"Targeting epidermal growth factor receptor: Central signaling kinase in lung cancer","volume":"80","author":"Yoshida T","year":"2010","unstructured":"T Yoshida, G Zhang, EB Haura, Targeting epidermal growth factor receptor: Central signaling kinase in lung cancer. Biochem Pharmacol 80, 613\u2013623 (2010).","journal-title":"Biochem Pharmacol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1056\/NEJM200104053441401","article-title":"Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia","volume":"344","author":"Druker BJ","year":"2001","unstructured":"BJ Druker, et al., Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344, 1031\u20131037 (2001).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa050753","article-title":"Erlotinib in previously treated non-small-cell lung cancer","volume":"353","author":"Shepherd FA","year":"2005","unstructured":"FA Shepherd, et al.; National Cancer Institute of Canada Clinical Trials Group, Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353, 123\u2013132 (2005).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1371\/journal.pmed.0020073","article-title":"Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain","volume":"2","author":"Pao W","year":"2005","unstructured":"W Pao, et al., Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2, e73 (2005).","journal-title":"PLoS Med"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.1038\/sj.onc.1206942","article-title":"Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias","volume":"22","author":"Shah NP","year":"2003","unstructured":"NP Shah, CL Sawyers, Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene 22, 7389\u20137395 (2003).","journal-title":"Oncogene"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"16266","DOI":"10.1073\/pnas.0608017103","article-title":"Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch","volume":"103","author":"Giuriato S","year":"2006","unstructured":"S Giuriato, et al., Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci USA 103, 16266\u201316271 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.1099480","article-title":"Overriding imatinib resistance with a novel ABL kinase inhibitor","volume":"305","author":"Shah NP","year":"2004","unstructured":"NP Shah, et al., Overriding imatinib resistance with a novel ABL kinase inhibitor. Science (New York, N.Y.) 305, 399\u2013401 (2004).","journal-title":"Science (New York, N.Y.)"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1182\/blood-2002-10-3091","article-title":"Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations","volume":"101","author":"Karlsson A","year":"2003","unstructured":"A Karlsson, et al., Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations. Blood 101, 2797\u20132803 (2003).","journal-title":"Blood"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"8109","DOI":"10.1128\/MCB.00404-06","article-title":"Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis","volume":"26","author":"Jang JW","year":"2006","unstructured":"JW Jang, RB Boxer, LA Chodosh, Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol Cell Biol 26, 8109\u20138121 (2006).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"7804","DOI":"10.1073\/pnas.90.16.7804","article-title":"The ornithine decarboxylase gene is a transcriptional target of c-Myc","volume":"90","author":"Bello-Fernandez C","year":"1993","unstructured":"C Bello-Fernandez, G Packham, JL Cleveland, The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc Natl Acad Sci USA 90, 7804\u20137808 (1993).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_31_2","first-page":"6318","article-title":"Bax is a transcriptional target and mediator of c-myc-induced apoptosis","volume":"60","author":"Mitchell KO","year":"2000","unstructured":"KO Mitchell, et al., Bax is a transcriptional target and mediator of c-myc-induced apoptosis. Cancer Res 60, 6318\u20136325 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/nar\/28.2.446","article-title":"Myc induces the nucleolin and BN51 genes: Possible implications in ribosome biogenesis","volume":"28","author":"Greasley PJ","year":"2000","unstructured":"PJ Greasley, C Bonnard, B Amati, Myc induces the nucleolin and BN51 genes: Possible implications in ribosome biogenesis. Nucleic Acids Res 28, 446\u2013453 (2000).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"5242","DOI":"10.1073\/pnas.0801197105","article-title":"Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras","volume":"105","author":"Podsypanina K","year":"2008","unstructured":"K Podsypanina, K Politi, LJ Beverly, HE Varmus, Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proc Natl Acad Sci USA 105, 5242\u20135247 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"5547","DOI":"10.1073\/pnas.89.12.5547","article-title":"Tight control of gene expression in mammalian cells by tetracycline-responsive promoters","volume":"89","author":"Gossen M","year":"1992","unstructured":"M Gossen, H Bujard, Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89, 5547\u20135551 (1992).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1038\/sj.onc.1204595","article-title":"Translocations involving c-myc and c-myc function","volume":"20","author":"Boxer LM","year":"2001","unstructured":"LM Boxer, CV Dang, Translocations involving c-myc and c-myc function. Oncogene 20, 5595\u20135610 (2001).","journal-title":"Oncogene"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1182\/blood.V95.6.2104","article-title":"c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover","volume":"95","author":"Bahram F","year":"2000","unstructured":"F Bahram, N von der Lehr, C Cetinkaya, LG Larsson, c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover. Blood 95, 2104\u20132110 (2000).","journal-title":"Blood"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1101\/gad.1450406","article-title":"c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia\/lymphoma","volume":"20","author":"Weng AP","year":"2006","unstructured":"AP Weng, et al., c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia\/lymphoma. Genes Dev 20, 2096\u20132109 (2006).","journal-title":"Genes Dev"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1097-2765(00)80308-1","article-title":"Ras enhances Myc protein stability","volume":"3","author":"Sears R","year":"1999","unstructured":"R Sears, G Leone, J DeGregori, JR Nevins, Ras enhances Myc protein stability. Mol Cell 3, 169\u2013179 (1999).","journal-title":"Mol Cell"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1126\/science.281.5382.1509","article-title":"Identification of c-MYC as a target of the APC pathway","volume":"281","author":"He TC","year":"1998","unstructured":"TC He, et al., Identification of c-MYC as a target of the APC pathway. Science 281, 1509\u20131512 (1998).","journal-title":"Science"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.1102160","article-title":"Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia","volume":"306","author":"Weng AP","year":"2004","unstructured":"AP Weng, et al., Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306, 269\u2013271 (2004).","journal-title":"Science"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1101\/gad.1793709","article-title":"Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A","volume":"23","author":"Yashiro-Ohtani Y","year":"2009","unstructured":"Y Yashiro-Ohtani, et al., Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes Dev 23, 1665\u20131676 (2009).","journal-title":"Genes Dev"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.febslet.2004.07.055","article-title":"Rank products: A simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments","volume":"573","author":"Breitling R","year":"2004","unstructured":"R Breitling, P Armengaud, A Amtmann, P Herzyk, Rank products: A simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573, 83\u201392 (2004).","journal-title":"FEBS Lett"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"18261","DOI":"10.1073\/pnas.0606108103","article-title":"NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth","volume":"103","author":"Palomero T","year":"2006","unstructured":"T Palomero, et al., NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci USA 103, 18261\u201318266 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"8022","DOI":"10.1128\/MCB.01091-06","article-title":"Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc","volume":"26","author":"Sharma VM","year":"2006","unstructured":"VM Sharma, et al., Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol Cell Biol 26, 8022\u20138031 (2006).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1172\/JCI33320","article-title":"Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf\/p53 pathway lesions but not p16 Ink4a loss","volume":"118","author":"Debies MT","year":"2008","unstructured":"MT Debies, et al., Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf\/p53 pathway lesions but not p16 Ink4a loss. J Clin Invest 118, 51\u201363 (2008).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ccr.2010.10.002","article-title":"CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation","volume":"18","author":"Rakhra K","year":"2010","unstructured":"K Rakhra, et al., CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485\u2013498 (2010).","journal-title":"Cancer Cell"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","volume":"316","author":"Engelman JA","year":"2007","unstructured":"JA Engelman, et al., MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science (New York, N.Y.) 316, 1039\u20131043 (2007).","journal-title":"Science (New York, N.Y.)"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/nature09627","article-title":"COT drives resistance to RAF inhibition through MAP kinase pathway reactivation","volume":"468","author":"Johannessen CM","year":"2010","unstructured":"CM Johannessen, et al., COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968\u2013972 (2010).","journal-title":"Nature"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nature09626","article-title":"Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation","volume":"468","author":"Nazarian R","year":"2010","unstructured":"R Nazarian, et al., Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973\u2013977 (2010).","journal-title":"Nature"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1107303108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T03:51:39Z","timestamp":1654573899000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1107303108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,3]]},"references-count":49,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2011,10,18]]}},"alternative-id":["10.1073\/pnas.1107303108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1107303108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,3]]},"assertion":[{"value":"2011-10-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}