title: Inhibitory Effects of Dopamine Receptor D1Agonist on Mammary Tumor and Bone Metastasis.
abstract: Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis.
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.|Department of Medical Physics &Engineering Osaka University Graduate School of Medicine Suita, Osaka 565-0871, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.|Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China.
authors.forename: Shengzhi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.|Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Andy
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Qiaoqiao
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Na
authors.affiliation: Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China.
authors.forename: Bai-Yan
authors.initials: BY
authors.lastname: Li
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.affiliation: Department of Medical Physics &Engineering Osaka University Graduate School of Medicine Suita, Osaka 565-0871, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koizumi
authors.affiliation: Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Liangying
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Aihua
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, Simon Cancer Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Nakshatri
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms; D002460:Cell Line; D045744:Cell Line, Tumor; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1