Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.

The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual funct...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elisabeth Silden, Sigrun M Hjelle, Line Wergeland, André Sulen, Vibeke Andresen, Jean-Christophe Bourdon, David R Micklem, Emmet McCormack, Bjørn Tore Gjertsen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14b0caf52b21424191e729f001e39752
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:14b0caf52b21424191e729f001e39752
record_format	dspace
spelling	oai:doaj.org-article:14b0caf52b21424191e729f001e397522021-11-18T07:58:01ZExpression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.1932-620310.1371/journal.pone.0056276https://doaj.org/article/14b0caf52b21424191e729f001e397522013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409163/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1)), Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(P)H quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.Elisabeth SildenSigrun M HjelleLine WergelandAndré SulenVibeke AndresenJean-Christophe BourdonDavid R MicklemEmmet McCormackBjørn Tore GjertsenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56276 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisabeth Silden Sigrun M Hjelle Line Wergeland André Sulen Vibeke Andresen Jean-Christophe Bourdon David R Micklem Emmet McCormack Bjørn Tore Gjertsen Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
description	The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1)), Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(P)H quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.
format	article
author	Elisabeth Silden Sigrun M Hjelle Line Wergeland André Sulen Vibeke Andresen Jean-Christophe Bourdon David R Micklem Emmet McCormack Bjørn Tore Gjertsen
author_facet	Elisabeth Silden Sigrun M Hjelle Line Wergeland André Sulen Vibeke Andresen Jean-Christophe Bourdon David R Micklem Emmet McCormack Bjørn Tore Gjertsen
author_sort	Elisabeth Silden
title	Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
title_short	Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
title_full	Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
title_fullStr	Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
title_full_unstemmed	Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.
title_sort	expression of tp53 isoforms p53β or p53γ enhances chemosensitivity in tp53(null) cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/14b0caf52b21424191e729f001e39752
work_keys_str_mv	AT elisabethsilden expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT sigrunmhjelle expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT linewergeland expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT andresulen expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT vibekeandresen expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT jeanchristophebourdon expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT davidrmicklem expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT emmetmccormack expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines AT bjørntoregjertsen expressionoftp53isoformsp53borp53genhanceschemosensitivityintp53nullcelllines
_version_	1718422713120325632

Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.

Ejemplares similares