Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer

Borcherding, Dana C.; Tong, Wilson; Hugo, Eric R.; Barnard, David F; Fox, Sejal R.; LaSance, Kathleen; Shaughnessy, Elizabeth; Ben‐Jonathan, Nira

doi:10.1038/onc.2015.369

Cited by 75 publications

(100 citation statements)

References 47 publications

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“…It is reported that a partial agonist of DRD1-like receptors, Fenoldopam, causes tumor shrinkage in the mouse xenograft model through the cGMP/protein kinase G (PKG) pathway27. We also observed reduction in cell proliferation in 4T1.2 cells (Suppl.…”

Section: Discussionmentioning

confidence: 56%

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Minami¹,

Liu²,

Liu³

et al. 2017

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 56%

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Minami¹,

Liu²,

Liu³

et al. 2017

Sci Rep

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“…Expression of DA D 1 receptors was found in 30% of patients with primary breast carcinomas and was associated with larger tumors, higher tumor grades, node metastasis, and shorter patient survival. However, in vitro activation of the D 1 ‐receptor/cGMP/protein kinase G pathway suppressed cell viability, inhibited invasion and induced apoptosis (70). It seems counterintuitive that increased D 1 ‐receptor expression correlates positively with advanced disease, whereas D 1 ‐receptor activation results in apoptosis.…”

Section: Interaction Between Da and Angiogenesismentioning

confidence: 99%

“…Borcherding et al (70) hypothesized several mechanisms to explain the counterintuitive positive correlation between DA signaling and malignant behavior observed in vitro in human breast cancer cells, such as changes in the role of the D 1 receptor and the cGMP apoptotic pathway during tumor progression and metastatic stages of the disease. Mechanisms similar to these may also be applicable in malignant PCC and PGL.…”

Section: Da Synthesis and Hypoxia Are Linked In Pcc And Pglmentioning

confidence: 99%

Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma

et al. 2017

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Dopamine is a catecholamine that acts both as a neurotransmitter and as a hormone, exerting its functions dopamine (DA) receptors that are present in a broad variety of organs andcells throughout the body. In the circulation, DA is primarily stored in and transported by blood platelets. Recently, the important contribution of DA in the regulation of angiogenesis has been recognized. and studies have shown that DA inhibits angiogenesis through activation of the DA receptor type 2. Overproduction of catecholamines is the biochemical hallmark of pheochromocytoma (PCC) and paraganglioma (PGL). The increased production of DA has been shown to be an independent predictor of malignancy in these tumors. The precise relationship underlying the association between DA production and PCC and PGL behavior needs further clarification. Herein, we review the biochemical and physiologic aspects of DA with a focus on its relations with VEGF and hypoxia inducible factor related angiogenesis pathways, with special emphasis on DA producing PCC and PGL.-Osinga, T. E., Links, T. P., Dullaart, R. P. F., Pacak, K., van der Horst-Schrivers, A. N. A., Kerstens, M. N., Kema, I. P. Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma.

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“…Dopamine receptors (DRD1-5) mainly reside in the human brain, which play important roles in cancer tumorigenesis and progression [5][6][7][8][9]. DRD2 agonists inhibit the growth of lung cancer cells including NSCLC and small cell lung cancer [6,10,11].…”

Section: Introductionmentioning

confidence: 99%

Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-κB Signaling Pathway

Zhang

Deng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. Dopamine receptor D2 (DRD2) has multiple roles in clinical progression of NSCLC and functional maintenance of cancer cells. However, little is known about the molecular mechanism. Here, we clarified whether DRD2 inhibits lung cancer progression and identified the underlying downstream signaling. Methods: DRD2 mRNA and protein levels were detected in clinical specimens by qRT-PCR and immunohistochemistry, respectively. MTT and colony formation assays were applied to analyze cell proliferation. The underlying molecular mechanism was identified by dual luciferase, western blot, qRT-PCR, cAMP detection, immunoprecipitation, and chromatin immunoprecipitation assays. A murine NSCLC model was used to clarify the role of DRD2 in tumor cell proliferation. Results: We found that DRD2 ablated tumor cell growth. DRD2 expression in NSCLC tissues was lower than in adjacent normal lung tissues. Moreover, DRD2 mRNA and protein levels in NSCLC were negatively correlated with the tumor size, TNM status, and patient overall survival. In vitro experiments showed that disruption of DRD2 promoted the proliferation of NSCLC cell lines A549 and SK-MES-1 by inhibiting the NF-κB signaling pathway. Furthermore, DRD2 overexpression not only blocked lipopolysaccharide-induced A549 and SK-MES-1 cell proliferation and growth, but also inhibited the tumorigenesis in murine xenograft models. Conclusion: These results indicate that DRD2 may be a potential therapeutic target for lung cancer patients with high DRD2 expression by ablating the NF-κB signaling pathway.

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Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer

Cited by 75 publications

References 47 publications

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma

Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-κB Signaling Pathway

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