Inhibitory Effects of Dopamine Receptor D 1 Agonist on Mammary Tumor and Bone Metastasis

Kazumasa Minami, Shengzhi Liu, Yang Liu, Andy Chen, Qiaoqiao Wan, Sungsoo Na, Bai Yan Li, Nariaki Matsuura, Masahiko Koizumi, Yukun Yin, Liangying Gan, Aihua Xu, Jiliang Li, Harikrishna Nakshatri, Hiroki Yokota

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13 Scopus citations

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.

Original languageEnglish (US)
Article number45686
JournalScientific reports
Volume7
DOIs
StatePublished - Apr 4 2017

ASJC Scopus subject areas

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    Minami, K., Liu, S., Liu, Y., Chen, A., Wan, Q., Na, S., Li, B. Y., Matsuura, N., Koizumi, M., Yin, Y., Gan, L., Xu, A., Li, J., Nakshatri, H., & Yokota, H. (2017). Inhibitory Effects of Dopamine Receptor D 1 Agonist on Mammary Tumor and Bone Metastasis. Scientific reports, 7, [45686]. https://doi.org/10.1038/srep45686