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

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Advanced breast cancer presents challenges in treatment response.
• Dopamine (DA) exerts effects via G protein-coupled receptors.
• Dopamine type-1 receptors (D1Rs) are identified in breast cancer cells.

Purpose of the Study:

• To investigate D1R expression in breast cancer.
• To evaluate D1Rs as potential therapeutic targets.
• To assess the therapeutic potential of D1R activation.

Main Methods:

• Immunohistochemical analysis of D1R expression in 751 primary breast carcinomas.
• In vitro studies using breast cancer cell lines to assess D1R agonist effects on cell viability, invasion, and apoptosis.
• In vivo studies using mouse xenograft models treated with fenoldopam.
• Fluorescence imaging to detect D1R-expressing tumors and metastases.

Main Results:

• D1R expression was found in 30% of breast carcinomas, associated with adverse prognostic factors.
• D1R agonists suppressed breast cancer cell viability, invasion, and induced apoptosis via the cGMP/protein kinase G (PKG) pathway.
• Fenoldopam treatment significantly suppressed tumor growth in D1R-expressing xenografts, increasing necrosis and apoptosis.

Conclusions:

• D1R overexpression is linked to advanced breast cancer and poor patient outcomes.
• Activation of the D1R/cGMP/PKG pathway demonstrates anti-cancer effects in vitro and in vivo.
• Fenoldopam, an FDA-approved drug, shows promise for repurposing as a novel therapeutic for D1R-positive breast cancer.