Induction of senescence in primary glioblastoma cells by serum and TGFβ

Abstract Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncoge...

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Autores principales:	Ritesh Kumar, Alexander Gont, Theodore J. Perkins, Jennifer E. L. Hanson, Ian A. J. Lorimer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9600ca8f6ee94a838aaa5c94ff55151b
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spelling	oai:doaj.org-article:9600ca8f6ee94a838aaa5c94ff55151b2021-12-02T11:53:01ZInduction of senescence in primary glioblastoma cells by serum and TGFβ10.1038/s41598-017-02380-12045-2322https://doaj.org/article/9600ca8f6ee94a838aaa5c94ff55151b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02380-1https://doaj.org/toc/2045-2322Abstract Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence. Microarray expression analysis showed that 24 h serum exposure increased the expression of genes associated with the TGFβ pathway. Treatment of PriGO8A cells with TGFβ was sufficient to induce senescence in these cells. The response of PriGO8A cells to serum was dependent on basal expression of the TGFβ activator protein thrombospondin. Primary glioblastoma cells from three additional patients showed a variable ability to undergo senescence in response to serum. However all were able to undergo senescence in response to TGFβ, although for cells from one patient this required concomitant inhibition of Ras pathway signalling. Primary glioblastoma cells therefore retain a functional senescence program that is inducible by acute activation of the TGFβ signalling pathway.Ritesh KumarAlexander GontTheodore J. PerkinsJennifer E. L. HansonIan A. J. LorimerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ritesh Kumar Alexander Gont Theodore J. Perkins Jennifer E. L. Hanson Ian A. J. Lorimer Induction of senescence in primary glioblastoma cells by serum and TGFβ
description	Abstract Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence. Microarray expression analysis showed that 24 h serum exposure increased the expression of genes associated with the TGFβ pathway. Treatment of PriGO8A cells with TGFβ was sufficient to induce senescence in these cells. The response of PriGO8A cells to serum was dependent on basal expression of the TGFβ activator protein thrombospondin. Primary glioblastoma cells from three additional patients showed a variable ability to undergo senescence in response to serum. However all were able to undergo senescence in response to TGFβ, although for cells from one patient this required concomitant inhibition of Ras pathway signalling. Primary glioblastoma cells therefore retain a functional senescence program that is inducible by acute activation of the TGFβ signalling pathway.
format	article
author	Ritesh Kumar Alexander Gont Theodore J. Perkins Jennifer E. L. Hanson Ian A. J. Lorimer
author_facet	Ritesh Kumar Alexander Gont Theodore J. Perkins Jennifer E. L. Hanson Ian A. J. Lorimer
author_sort	Ritesh Kumar
title	Induction of senescence in primary glioblastoma cells by serum and TGFβ
title_short	Induction of senescence in primary glioblastoma cells by serum and TGFβ
title_full	Induction of senescence in primary glioblastoma cells by serum and TGFβ
title_fullStr	Induction of senescence in primary glioblastoma cells by serum and TGFβ
title_full_unstemmed	Induction of senescence in primary glioblastoma cells by serum and TGFβ
title_sort	induction of senescence in primary glioblastoma cells by serum and tgfβ
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9600ca8f6ee94a838aaa5c94ff55151b
work_keys_str_mv	AT riteshkumar inductionofsenescenceinprimaryglioblastomacellsbyserumandtgfb AT alexandergont inductionofsenescenceinprimaryglioblastomacellsbyserumandtgfb AT theodorejperkins inductionofsenescenceinprimaryglioblastomacellsbyserumandtgfb AT jenniferelhanson inductionofsenescenceinprimaryglioblastomacellsbyserumandtgfb AT ianajlorimer inductionofsenescenceinprimaryglioblastomacellsbyserumandtgfb
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Induction of senescence in primary glioblastoma cells by serum and TGFβ

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