title: The Correlation Between PARP1 and BRCA1 in AR Positive Triple-negative Breast Cancer.
abstract: Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression and thus cannot benefit from conventional hormonal or anti-HER2 targeted therapies. Anti-androgen therapy has shown a certain effect on androgen receptor (AR) positive TNBC. The emerging researches have proved that poly (ADP-ribose) polymerase (PARP) inhibitor is effective in BRCA1-deficient breast cancers. We demonstrated that combination of AR antagonist (bicalutamide) and PARP inhibitor (ABT-888) could inhibit cell viability and induce cell apoptosis significantly whatever in vitro or in vivo setting in AR-positive TNBC. Previous studies have proved that both BRCA1 and PARP1 have close connections with AR in prostate cancer. We explored the correlation among AR, PARP1 and BRCA1 in TNBC for the first time. After BRCA1 overexpression, the expression of AR and PARP1 were decreased in mRNA and protein levels. Additionally, AR positively regulated PARP1 while PARP1 also up-regulated AR expression in vitro. We also confirmed BRCA1 expression was negatively correlated with AR and PARP1 in TNBC patients using a tissue microarray with TNBC patient samples. These results suggest that the combination of bicalutamide and PARP inhibitor may be a potential strategy for TNBC patients and merits further evaluation.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Zijia
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001562:Benzimidazoles / Q000627:therapeutic use; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009570:Nitriles / Q000627:therapeutic use; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014105:Tosyl Compounds / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000813:Anilides; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D001562:Benzimidazoles; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C521013:veliparib; C053541:bicalutamide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: AR; BRCA1; PARP1; combination therapy; triple-negative breast cancer.