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

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...

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Autores principales: da Costa, Adilson, Bonner, Michael Y., Rao, Shikha, Gilbert, Linda, Sasaki, Maiko, Elsey, Justin, MacKelfresh, Jamie, Arbiser, Jack L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072444/
https://www.ncbi.nlm.nih.gov/pubmed/32046305
http://dx.doi.org/10.3390/cancers12020395
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author da Costa, Adilson
Bonner, Michael Y.
Rao, Shikha
Gilbert, Linda
Sasaki, Maiko
Elsey, Justin
MacKelfresh, Jamie
Arbiser, Jack L.
author_facet da Costa, Adilson
Bonner, Michael Y.
Rao, Shikha
Gilbert, Linda
Sasaki, Maiko
Elsey, Justin
MacKelfresh, Jamie
Arbiser, Jack L.
author_sort da Costa, Adilson
collection PubMed
description 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.
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spelling pubmed-70724442020-03-19 Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells da Costa, Adilson Bonner, Michael Y. Rao, Shikha Gilbert, Linda Sasaki, Maiko Elsey, Justin MacKelfresh, Jamie Arbiser, Jack L. Cancers (Basel) Article 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. MDPI 2020-02-08 /pmc/articles/PMC7072444/ /pubmed/32046305 http://dx.doi.org/10.3390/cancers12020395 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
da Costa, Adilson
Bonner, Michael Y.
Rao, Shikha
Gilbert, Linda
Sasaki, Maiko
Elsey, Justin
MacKelfresh, Jamie
Arbiser, Jack L.
Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title_full Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title_fullStr Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title_full_unstemmed Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title_short Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells
title_sort establishment of a temperature-sensitive model of oncogene-induced senescence in angiosarcoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072444/
https://www.ncbi.nlm.nih.gov/pubmed/32046305
http://dx.doi.org/10.3390/cancers12020395
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