title: Decreased miR-206 expression in BRCA1 wild-type triple-negative breast cancer cells after concomitant treatment with gemcitabine and a Poly(ADP-ribose) polymerase-1 inhibitor.
abstract: No targeted-therapy has been established for triple-negative breast cancer accompanied by mutations in breast cancer susceptibility gene1 (BRCA1) mutation. In the present study, using BRCA1 wild-type cells (MDA-MB-231) and BRCA1-mutated cells (MDA-MB-436), we investigated miRNA expression and apoptosis on day 1 after addition of gemcitabine-alone and in combination with poly ADP-ribose polymerase-1 (PARP1) inhibitor. After drug treatment, there were significantly fewer apoptotic BRCA1 wild-type cells than BRCA1-mutated cells. Expression of miRNA-26a, -29b, -100, and -148a increased in BRCA1 wild-type cells exposed to gemcitabine-alone and in combination with the PARP1 inhibitor. The addition of PARP1 inhibitor reduced miR-206 expression in BRCA1 wild-type cells but increased it in BRCA1-mutated cells. It was suggested that miR-206 serves as a target molecule of PARP1 inhibitor combination therapy for BRCA1 wild-type triple-negative breast cancer cells.
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan sakiko@med.showa-u.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Kameda Medical Center, Breast Center, Kamogawa City, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsunoda
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Udaka
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Oyamada
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Oguchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D004791:Enzyme Inhibitors; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: BRCA1; PARP1; TNBC; breast cancer cells; miRNA