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Open AccessArticle

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells

1
Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA
2
Department of Post-Graduate Studies, Instituto de Assistência Médica ao Servidor Público Estadual, Sao Paulo, SP 04029-000, Brazil
3
Department of Medical Biochemistry & Biophysics, Karolinska Institutet, 17177 Solna, Sweden
4
Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
5
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
6
Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 395; https://doi.org/10.3390/cancers12020395
Received: 11 December 2019 / Revised: 31 January 2020 / Accepted: 1 February 2020 / Published: 8 February 2020
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 °C, 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 °C. 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. View Full-Text
Keywords: driver mutations; angiosarcoma; vascular proliferation; oncogenic Hras driver mutations; angiosarcoma; vascular proliferation; oncogenic Hras
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MDPI and ACS Style

da Costa, A.; Bonner, M.Y.; Rao, S.; Gilbert, L.; Sasaki, M.; Elsey, J.; MacKelfresh, J.; Arbiser, J.L. Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells. Cancers 2020, 12, 395.

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