Dopamine receptor-1 in breast cancer: Expression, signaling and therapeutic targeting

13^th Asia-Pacific Oncologists Annual Meeting

October 17-19, 2016 Kuala Lumpur, Malaysia

Nira Ben-Jonathan

University of Cincinnati, USA

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Dopamine (DA) is a catecholamine which binds to five G-protein-coupled membrane receptors. We discovered overexpression of DA type-1 receptors (D1R) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas and this expression was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. Unexpectedly, DA and D1R agonists were found to signal through the cGMP/protein kinase G (PKG) pathway. Several selective activators of this pathway suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist which does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenograft by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA-approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.

Biography :

Email: benjonn@ucmail.uc.edu