Oncotarget

Research Papers:

Rad51 supports triple negative breast cancer metastasis.

Adrian P. Wiegmans, Fares Al-Ejeh, Nicole Chee, Pei-Yi Yap, Julia J. Gorski, Leonard Da Silva, Emma Bolderson, Georgia Chenevix-Trench, Robin Anderson, Peter T. Simpson, Sunil R. Lakhani and Kum Kum Khanna _

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Oncotarget. 2014; 5:3261-3272. https://doi.org/10.18632/oncotarget.1923

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Abstract

Adrian P Wiegmans1, Fares Al-Ejeh1, Nicole Chee1, Pei-Yi Yap1, Julia J Gorski2, Leonard Da Silva3,4, Emma Bolderson5, Georgia Chenevix-Trench6, Robin Anderson7,8, Peter T Simpson3, Sunil R Lakhani3,4,9 and Kum Kum Khanna1

1 QIMR Berghofer Medical Research Institute, Signal Transduction Laboratory, Herston Rd, Herston QLD 4006, Australia

2 Queens University Belfast, Dentistry and Biomedical Science, Lisburn Rd, Belfast, BT5 7BL, UK

3 The University of Queensland, UQ Centre for Clinical Research, Herston, Brisbane, QLD 4006, Australia

4 The University of Queensland, School of Medicine, Herston, Brisbane, QLD 4006, Australia

5 The University of Queensland, Institute of Health and Biomedical Innovation, TRI, Woolloongabba, Brisbane, QLD 4102, Australia

6 Cancer Genetics Laboratory, Queensland Institute of Medical Research, Herston Rd, Herston QLD 4006, Australia

7 Metastasis Research Laboratory, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne Vic 3002, Australia

8 Department of Oncology, Sir Peter MacCallum Cancer Centre, The University of Melbourne, Parkville Vic 3052, Australia

9 Pathology Queensland: The Royal Brisbane & Women’s Hospital, Brisbane, Herston QLD 4006, Australia

Correspondence:

Kum Kum Khanna, email:

Keywords: RAD51, metastasis, breast cancer, DNA damage, c/EBPbeta, metastatic cancer.

Received: March 04, 2014 Accepted: April 25, 2014 Published: April 27, 2014

Abstract

In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months.


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