A.T. Alshareeda
KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer
Alshareeda, A.T.; Negm, O.H.; Green, A.R.; Nolan, C.C.; Tighe, P.; Albarakati, N.; Sultana, R.; Madhusudan, S.; Ellis, I.O.; Rakha, E.A.
Authors
OLA NEGM ola.negm@nottingham.ac.uk
Assistant Professor
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
C.C. Nolan
PATRICK TIGHE paddy.tighe@nottingham.ac.uk
Professor of Molecular Immunology
N. Albarakati
R. Sultana
SRINIVASAN MADHUSUDAN srinivasan.madhusudan@nottingham.ac.uk
Professor of Medical Oncology
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
Abstract
Background: It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin a-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC.
Methods: A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry.
Results: KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, gammaH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P less than 0.0001), but this effect was not independent of other prognostic variables.
Conclusions: This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.
Citation
Alshareeda, A., Negm, O., Green, A., Nolan, C., Tighe, P., Albarakati, N., …Rakha, E. (2015). KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. British Journal of Cancer, 112(12), 1929–1937. https://doi.org/10.1038/bjc.2015.165
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 31, 2015 |
Online Publication Date | May 19, 2015 |
Publication Date | Jun 9, 2015 |
Deposit Date | May 29, 2018 |
Publicly Available Date | Mar 29, 2024 |
Print ISSN | 0007-0920 |
Publisher | Cancer Research UK |
Peer Reviewed | Peer Reviewed |
Volume | 112 |
Issue | 12 |
Pages | 1929–1937 |
DOI | https://doi.org/10.1038/bjc.2015.165 |
Public URL | http://www.ncbi.nlm.nih.gov/pubmed/25989275 |
Publisher URL | https://www.nature.com/articles/bjc2015165 |
Files
Bjc2015165
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Publisher Licence URL
https://creativecommons.org/licenses/by-nc/4.0/
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