title: Rad51 supports triple negative breast cancer metastasis.
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.
authors.affiliation: QIMR Berghofer Medical Research Institute, Signal Transduction Laboratory, Herston Rd, Herston QLD 4006, Australia.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Wiegmans
authors.forename: Fares
authors.initials: F
authors.lastname: Al-Ejeh
authors.forename: Nicole
authors.initials: N
authors.lastname: Chee
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Yap
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Gorski
authors.forename: Leonard
authors.initials: L
authors.lastname: Da Silva
authors.forename: Emma
authors.initials: E
authors.lastname: Bolderson
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Robin
authors.initials: R
authors.lastname: Anderson
authors.forename: Peter T
authors.initials: PT
authors.lastname: Simpson
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051135:Rad51 Recombinase