Evaluation of Gene Expression Data From Cybrids and Tumours Highlights Elevated

NDRG1 breast cancer cybrids

Journal

Breast cancer : basic and clinical research
ISSN: 1178-2234
Titre abrégé: Breast Cancer (Auckl)
Pays: United States
ID NLM: 101474356

Informations de publication

Date de publication:
2020
Historique:
received: 27 03 2020
accepted: 20 05 2020
entrez: 3 7 2020
pubmed: 3 7 2020
medline: 3 7 2020
Statut: epublish

Résumé

Triple-negative breast cancer is an aggressive type of breast cancer with high risk of recurrence. It is still poorly understood and lacks any targeted therapy, which makes it difficult to treat. Thus, it is important to understand the underlying mechanisms and pathways that are dysregulated in triple-negative breast cancer. To investigate the role of mitochondria in triple-negative breast cancer progression, we analysed previously reported gene expression data from triple-negative breast cancer cybrids with SUM-159 as the nuclear donor cell and SUM-159 or A1N4 (c-SUM-159, c-A1N4) as the mitochondrial donor cells and with 143B as the nuclear donor cell and MCF-10A or MDA-MB-231 (c-MCF-10A, c-MDA-MB-231) as the mitochondrial donor cells. The role of potential biomarkers in cell proliferation and migration was examined in SUM-159 and MDA-MB-231 cells using sulforhodamine B and wound healing assays. Rank product analysis of cybrid gene expression data identified 149 genes which were significantly up-regulated in the cybrids with mitochondria from the cancer cell line. Analysis of previously reported breast tumour gene expression datasets confirmed 9 of the 149 genes were amplified, up-regulated, or down-regulated in more than 10% of the patients. The genes included These results indicate that mitochondria-regulated nuclear gene expression helps breast cancer cells survive and proliferate, consistent with previous work focusing on an Src gene signature which is mitochondria regulated and drives malignancy in breast cancer cybrids. This is the first study to show that mitochondria in triple-negative breast cancer mediate significant up-regulation of a number of genes, and silencing of

Sections du résumé

BACKGROUND BACKGROUND
Triple-negative breast cancer is an aggressive type of breast cancer with high risk of recurrence. It is still poorly understood and lacks any targeted therapy, which makes it difficult to treat. Thus, it is important to understand the underlying mechanisms and pathways that are dysregulated in triple-negative breast cancer.
METHODS METHODS
To investigate the role of mitochondria in triple-negative breast cancer progression, we analysed previously reported gene expression data from triple-negative breast cancer cybrids with SUM-159 as the nuclear donor cell and SUM-159 or A1N4 (c-SUM-159, c-A1N4) as the mitochondrial donor cells and with 143B as the nuclear donor cell and MCF-10A or MDA-MB-231 (c-MCF-10A, c-MDA-MB-231) as the mitochondrial donor cells. The role of potential biomarkers in cell proliferation and migration was examined in SUM-159 and MDA-MB-231 cells using sulforhodamine B and wound healing assays.
RESULTS RESULTS
Rank product analysis of cybrid gene expression data identified 149 genes which were significantly up-regulated in the cybrids with mitochondria from the cancer cell line. Analysis of previously reported breast tumour gene expression datasets confirmed 9 of the 149 genes were amplified, up-regulated, or down-regulated in more than 10% of the patients. The genes included
CONCLUSIONS CONCLUSIONS
These results indicate that mitochondria-regulated nuclear gene expression helps breast cancer cells survive and proliferate, consistent with previous work focusing on an Src gene signature which is mitochondria regulated and drives malignancy in breast cancer cybrids. This is the first study to show that mitochondria in triple-negative breast cancer mediate significant up-regulation of a number of genes, and silencing of

Identifiants

pubmed: 32612361
doi: 10.1177/1178223420934447
pii: 10.1177_1178223420934447
pmc: PMC7309340
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1178223420934447

Informations de copyright

© The Author(s) 2020.

Déclaration de conflit d'intérêts

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Auteurs

Akanksha Mishra (A)

Applied Bioinformatics of Cancer, Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Maria Bonello (M)

Applied Bioinformatics of Cancer, Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Division of Pathology, The University of Edinburgh, Edinburgh, UK.

Adam Byron (A)

Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Simon P Langdon (SP)

Division of Pathology, The University of Edinburgh, Edinburgh, UK.

Andrew H Sims (AH)

Applied Bioinformatics of Cancer, Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Classifications MeSH