Cargando…

Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing

PTEN is among the most commonly mutated tumor suppressor genes in human cancer. However, studying the role of PTEN in the pathogenesis of cancer has been limited, in part, by the paucity of human cell-based isogenic systems that faithfully model PTEN loss. In an effort to remedy this problem, gene e...

Descripción completa

Detalles Bibliográficos
Autores principales: Hill, Victoria K., Kim, Jung-Sik, James, C. David, Waldman, Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413031/
https://www.ncbi.nlm.nih.gov/pubmed/28464039
http://dx.doi.org/10.1371/journal.pone.0176683
_version_ 1783233122499821568
author Hill, Victoria K.
Kim, Jung-Sik
James, C. David
Waldman, Todd
author_facet Hill, Victoria K.
Kim, Jung-Sik
James, C. David
Waldman, Todd
author_sort Hill, Victoria K.
collection PubMed
description PTEN is among the most commonly mutated tumor suppressor genes in human cancer. However, studying the role of PTEN in the pathogenesis of cancer has been limited, in part, by the paucity of human cell-based isogenic systems that faithfully model PTEN loss. In an effort to remedy this problem, gene editing was used to correct an endogenous mutant allele of PTEN in two human glioblastoma multiforme (GBM) cell lines– 42MGBA and T98G. PTEN correction resulted in reduced cellular proliferation that was Akt-dependent in 42MGBA cells and Akt-independent in T98G cells. This is the first report of human cancer cell lines in which mutant PTEN has been corrected by gene editing. The isogenic sets of gene edited cell lines reported here will likely prove useful for further study of PTEN mutations in the pathogenesis of cancer, and for the discovery and validation of novel therapeutics targeting the PTEN pathway.
format Online
Article
Text
id pubmed-5413031
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-54130312017-05-14 Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing Hill, Victoria K. Kim, Jung-Sik James, C. David Waldman, Todd PLoS One Research Article PTEN is among the most commonly mutated tumor suppressor genes in human cancer. However, studying the role of PTEN in the pathogenesis of cancer has been limited, in part, by the paucity of human cell-based isogenic systems that faithfully model PTEN loss. In an effort to remedy this problem, gene editing was used to correct an endogenous mutant allele of PTEN in two human glioblastoma multiforme (GBM) cell lines– 42MGBA and T98G. PTEN correction resulted in reduced cellular proliferation that was Akt-dependent in 42MGBA cells and Akt-independent in T98G cells. This is the first report of human cancer cell lines in which mutant PTEN has been corrected by gene editing. The isogenic sets of gene edited cell lines reported here will likely prove useful for further study of PTEN mutations in the pathogenesis of cancer, and for the discovery and validation of novel therapeutics targeting the PTEN pathway. Public Library of Science 2017-05-02 /pmc/articles/PMC5413031/ /pubmed/28464039 http://dx.doi.org/10.1371/journal.pone.0176683 Text en © 2017 Hill et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hill, Victoria K.
Kim, Jung-Sik
James, C. David
Waldman, Todd
Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title_full Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title_fullStr Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title_full_unstemmed Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title_short Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing
title_sort correction of pten mutations in glioblastoma cell lines via aav-mediated gene editing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413031/
https://www.ncbi.nlm.nih.gov/pubmed/28464039
http://dx.doi.org/10.1371/journal.pone.0176683
work_keys_str_mv AT hillvictoriak correctionofptenmutationsinglioblastomacelllinesviaaavmediatedgeneediting
AT kimjungsik correctionofptenmutationsinglioblastomacelllinesviaaavmediatedgeneediting
AT jamescdavid correctionofptenmutationsinglioblastomacelllinesviaaavmediatedgeneediting
AT waldmantodd correctionofptenmutationsinglioblastomacelllinesviaaavmediatedgeneediting