{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:19:12Z","timestamp":1767205152380,"version":"build-2238731810"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T00:00:00Z","timestamp":1581120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR47901"],"award-info":[{"award-number":["AR47901"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007217","name":"Health Services Research and Development","doi-asserted-by":"publisher","award":["I01 BX002926-05"],"award-info":[{"award-number":["I01 BX002926-05"]}],"id":[{"id":"10.13039\/100007217","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperature-sensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 \u00b0C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonproliferative state in the constant presence of a driver oncogene, SVR cells were cultivated for 24 and 48 h and compared with SVR cells at 37 \u00b0C. Cells were evaluated by Western Blot (WB) gene chip microarray (GC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Upon evaluation, a novel phenotype was observed in endothelial cells after switching off the large T antigen. This phenotype was characterized by Notch activation, downregulation of p38 phosphorylation, downregulation of the master immune switch IRF7, and downregulation of hnRNP A0. Switching off proliferative signaling may result in immune privilege and Notch activation, which may account, in part, for the survival of common skin lesions.<\/jats:p>","DOI":"10.3390\/cancers12020395","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T11:48:51Z","timestamp":1581335331000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Adilson","family":"da Costa","sequence":"first","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Post-Graduate Studies, Instituto de Assist\u00eancia M\u00e9dica ao Servidor P\u00fablico Estadual, Sao Paulo 04029-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bonner","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry &amp; Biophysics, Karolinska Institutet, 17177 Solna, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shikha","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-4365","authenticated-orcid":false,"given":"Maiko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Elsey","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"MacKelfresh","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Arbiser","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA"},{"name":"Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/cncr.21721","article-title":"K-ras mutations in incident sporadic colorectal adenomas","volume":"106","author":"Barry","year":"2006","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1053\/j.gastro.2006.08.038","article-title":"High prevalence of sessile serrated adenomas with BRAF mutations: A prospective study of patients undergoing colonoscopy","volume":"131","author":"Spring","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/01.cmr.0000215035.38436.87","article-title":"BRAF somatic mutations in malignant melanoma and melanocytic naevi","volume":"16","author":"Thomas","year":"2006","journal-title":"Melanoma Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/hmg\/ddi127","article-title":"Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans","volume":"14","author":"Logie","year":"2005","journal-title":"Hum. 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