High Expression of PPM1D Induces Tumors Phenotypically Similar to TP53 Loss-of-Function Mutations in Mice

PPM1D is a negative regulator of p53 and genomic aberrations resulting in increased activity of PPM1D have been observed in cancers of different origins, indicating that PPM1D has oncogenic properties. We established a transgenic mouse model o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jelena Milosevic, Susanne Fransson, Miklos Gulyas, Thale K. Olsen, Gabriel Gallo-Oller, Diana Treis, Lotta H. M. Elfman, Margareta Wilhelm, Tommy Martinsson, Ninib Baryawno, Per Kogner, John Inge Johnsen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>PPM1D</i> p53 genetically engineered mouse model adenocarcinoma lymphoma neuroblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4e7642724943438284674a8797264157
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4e7642724943438284674a8797264157
record_format	dspace
spelling	oai:doaj.org-article:4e7642724943438284674a87972641572021-11-11T15:33:43ZHigh Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice10.3390/cancers132154932072-6694https://doaj.org/article/4e7642724943438284674a87972641572021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5493https://doaj.org/toc/2072-6694<i>PPM1D</i> is a negative regulator of p53 and genomic aberrations resulting in increased activity of <i>PPM1D</i> have been observed in cancers of different origins, indicating that <i>PPM1D</i> has oncogenic properties. We established a transgenic mouse model overexpressing <i>PPM1D</i> and showed that these mice developed a wide variety of cancers. <i>PPM1D</i>-expressing mice developed tumors phenotypically and genetically similar to tumors in mice with dysfunctional p53. T-cell lymphoblastic lymphoma was the most frequent cancer observed in these mice (55%) followed by adenocarcinomas (24%), leukemia (12%) and other solid tumors including neuroblastoma. Characterization of T-cell lymphomas in mice overexpressing <i>PPM1D</i> demonstrates <i>Pten</i>-deletion and p53-accumulation similar to mice with p53 loss-of-function. Also, <i>Notch1</i> mutations which are recurrently observed in T-cell acute lymphoblastic lymphoma (T-ALL) were frequently detected in <i>PPM1D-</i>transgenic mice. Hence, <i>PPM1D</i> acts as an oncogenic driver in connection with cellular stress, suggesting that the <i>PPM1D</i> gene status and expression levels should be investigated in <i>TP53</i> wild-type tumors.Jelena MilosevicSusanne FranssonMiklos GulyasThale K. OlsenGabriel Gallo-OllerDiana TreisLotta H. M. ElfmanMargareta WilhelmTommy MartinssonNinib BaryawnoPer KognerJohn Inge JohnsenMDPI AGarticle<i>PPM1D</i>p53genetically engineered mouse modeladenocarcinomalymphomaneuroblastomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5493, p 5493 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>PPM1D</i> p53 genetically engineered mouse model adenocarcinoma lymphoma neuroblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	<i>PPM1D</i> p53 genetically engineered mouse model adenocarcinoma lymphoma neuroblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jelena Milosevic Susanne Fransson Miklos Gulyas Thale K. Olsen Gabriel Gallo-Oller Diana Treis Lotta H. M. Elfman Margareta Wilhelm Tommy Martinsson Ninib Baryawno Per Kogner John Inge Johnsen High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
description	<i>PPM1D</i> is a negative regulator of p53 and genomic aberrations resulting in increased activity of <i>PPM1D</i> have been observed in cancers of different origins, indicating that <i>PPM1D</i> has oncogenic properties. We established a transgenic mouse model overexpressing <i>PPM1D</i> and showed that these mice developed a wide variety of cancers. <i>PPM1D</i>-expressing mice developed tumors phenotypically and genetically similar to tumors in mice with dysfunctional p53. T-cell lymphoblastic lymphoma was the most frequent cancer observed in these mice (55%) followed by adenocarcinomas (24%), leukemia (12%) and other solid tumors including neuroblastoma. Characterization of T-cell lymphomas in mice overexpressing <i>PPM1D</i> demonstrates <i>Pten</i>-deletion and p53-accumulation similar to mice with p53 loss-of-function. Also, <i>Notch1</i> mutations which are recurrently observed in T-cell acute lymphoblastic lymphoma (T-ALL) were frequently detected in <i>PPM1D-</i>transgenic mice. Hence, <i>PPM1D</i> acts as an oncogenic driver in connection with cellular stress, suggesting that the <i>PPM1D</i> gene status and expression levels should be investigated in <i>TP53</i> wild-type tumors.
format	article
author	Jelena Milosevic Susanne Fransson Miklos Gulyas Thale K. Olsen Gabriel Gallo-Oller Diana Treis Lotta H. M. Elfman Margareta Wilhelm Tommy Martinsson Ninib Baryawno Per Kogner John Inge Johnsen
author_facet	Jelena Milosevic Susanne Fransson Miklos Gulyas Thale K. Olsen Gabriel Gallo-Oller Diana Treis Lotta H. M. Elfman Margareta Wilhelm Tommy Martinsson Ninib Baryawno Per Kogner John Inge Johnsen
author_sort	Jelena Milosevic
title	High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
title_short	High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
title_full	High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
title_fullStr	High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
title_full_unstemmed	High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice
title_sort	high expression of <i>ppm1d</i> induces tumors phenotypically similar to <i>tp53</i> loss-of-function mutations in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4e7642724943438284674a8797264157
work_keys_str_mv	AT jelenamilosevic highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT susannefransson highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT miklosgulyas highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT thalekolsen highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT gabrielgallooller highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT dianatreis highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT lottahmelfman highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT margaretawilhelm highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT tommymartinsson highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT ninibbaryawno highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT perkogner highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice AT johningejohnsen highexpressionofippm1diinducestumorsphenotypicallysimilartoitp53ilossoffunctionmutationsinmice
_version_	1718435177340862464

High Expression of <i>PPM1D</i> Induces Tumors Phenotypically Similar to <i>TP53</i> Loss-of-Function Mutations in Mice

Ejemplares similares