Cargando…
Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting
In order to be effective models to identify biomarkers of chemotherapy response, cancer cell lines require thorough characterization. In this study, we characterised the widely used high grade serous ovarian cancer (HGSOC) cell line NIH-OVCAR3 using bioinformatics, cytotoxicity assays and molecular/...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409137/ https://www.ncbi.nlm.nih.gov/pubmed/32709004 http://dx.doi.org/10.3390/cancers12071939 |
_version_ | 1783567995397734400 |
---|---|
author | Bradbury, Alice O’Donnell, Rachel Drew, Yvette Curtin, Nicola J. Sharma Saha, Sweta |
author_facet | Bradbury, Alice O’Donnell, Rachel Drew, Yvette Curtin, Nicola J. Sharma Saha, Sweta |
author_sort | Bradbury, Alice |
collection | PubMed |
description | In order to be effective models to identify biomarkers of chemotherapy response, cancer cell lines require thorough characterization. In this study, we characterised the widely used high grade serous ovarian cancer (HGSOC) cell line NIH-OVCAR3 using bioinformatics, cytotoxicity assays and molecular/functional analyses of DNA damage response (DDR) pathways in comparison to an ovarian cancer cell line panel. Bioinformatic analysis confirmed the HGSOC-like features of NIH-OVCAR3, including low mutation frequency, TP53 loss and high copy number alteration frequency similar to 201 HGSOCs analysed (TCGA). Cytotoxicity assays were performed for the standard of care chemotherapy, carboplatin, and DDR targeting drugs: rucaparib (a PARP inhibitor) and VE-821 (an ATR inhibitor). Interestingly, NIH-OVCAR3 cells showed sensitivity to carboplatin and rucaparib which was explained by functional loss of homologous recombination repair (HRR) identified by plasmid re-joining assay, despite the ability to form RAD51 foci and absence of mutations in HRR genes. NIH-OVCAR3 cells also showed high non-homologous end joining activity, which may contribute to HRR loss and along with genomic amplification in ATR and TOPBP1, could explain the resistance to VE-821. In summary, NIH-OVCAR3 cells highlight the complexity of HGSOCs and that genomic or functional characterization alone might not be enough to predict/explain chemotherapy response. |
format | Online Article Text |
id | pubmed-7409137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74091372020-08-26 Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting Bradbury, Alice O’Donnell, Rachel Drew, Yvette Curtin, Nicola J. Sharma Saha, Sweta Cancers (Basel) Article In order to be effective models to identify biomarkers of chemotherapy response, cancer cell lines require thorough characterization. In this study, we characterised the widely used high grade serous ovarian cancer (HGSOC) cell line NIH-OVCAR3 using bioinformatics, cytotoxicity assays and molecular/functional analyses of DNA damage response (DDR) pathways in comparison to an ovarian cancer cell line panel. Bioinformatic analysis confirmed the HGSOC-like features of NIH-OVCAR3, including low mutation frequency, TP53 loss and high copy number alteration frequency similar to 201 HGSOCs analysed (TCGA). Cytotoxicity assays were performed for the standard of care chemotherapy, carboplatin, and DDR targeting drugs: rucaparib (a PARP inhibitor) and VE-821 (an ATR inhibitor). Interestingly, NIH-OVCAR3 cells showed sensitivity to carboplatin and rucaparib which was explained by functional loss of homologous recombination repair (HRR) identified by plasmid re-joining assay, despite the ability to form RAD51 foci and absence of mutations in HRR genes. NIH-OVCAR3 cells also showed high non-homologous end joining activity, which may contribute to HRR loss and along with genomic amplification in ATR and TOPBP1, could explain the resistance to VE-821. In summary, NIH-OVCAR3 cells highlight the complexity of HGSOCs and that genomic or functional characterization alone might not be enough to predict/explain chemotherapy response. MDPI 2020-07-17 /pmc/articles/PMC7409137/ /pubmed/32709004 http://dx.doi.org/10.3390/cancers12071939 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 Bradbury, Alice O’Donnell, Rachel Drew, Yvette Curtin, Nicola J. Sharma Saha, Sweta Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title | Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title_full | Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title_fullStr | Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title_full_unstemmed | Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title_short | Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting |
title_sort | characterisation of ovarian cancer cell line nih-ovcar3 and implications of genomic, transcriptomic, proteomic and functional dna damage response biomarkers for therapeutic targeting |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409137/ https://www.ncbi.nlm.nih.gov/pubmed/32709004 http://dx.doi.org/10.3390/cancers12071939 |
work_keys_str_mv | AT bradburyalice characterisationofovariancancercelllinenihovcar3andimplicationsofgenomictranscriptomicproteomicandfunctionaldnadamageresponsebiomarkersfortherapeutictargeting AT odonnellrachel characterisationofovariancancercelllinenihovcar3andimplicationsofgenomictranscriptomicproteomicandfunctionaldnadamageresponsebiomarkersfortherapeutictargeting AT drewyvette characterisationofovariancancercelllinenihovcar3andimplicationsofgenomictranscriptomicproteomicandfunctionaldnadamageresponsebiomarkersfortherapeutictargeting AT curtinnicolaj characterisationofovariancancercelllinenihovcar3andimplicationsofgenomictranscriptomicproteomicandfunctionaldnadamageresponsebiomarkersfortherapeutictargeting AT sharmasahasweta characterisationofovariancancercelllinenihovcar3andimplicationsofgenomictranscriptomicproteomicandfunctionaldnadamageresponsebiomarkersfortherapeutictargeting |