L-Dopa-Decarboxylase (DDC) Is a Positive Prognosticator for Breast Cancer Patients and Epinephrine Regulates Breast Cancer Cell (MCF7 and T47D) Growth In Vitro According to Their Different Expression of Gi- Protein- Coupled Receptors.

Abstract

A coherence between thyroid dysfunction and breast cancer incidence exists. Thyroid hormone metabolites bind to TAAR1 (trace amine-associated receptor 1) and through that modulate the serotonergic and dopaminergic system. Catecholamines themselves are synthesized by the L-dopa decarboxylase (DDC). The aim of our study was to analyze the influence of catecholamines on the DDC expression in primary breast cancer patients and the role of DDC concerning overall survival (OS). DDC expression was analyzed by immunohistochemistry. The effect of epinephrine on the expression of DDC and the Gi- protein was analyzed on the protein level via Western blot. A viability assay was performed to test the metabolic cell viability. The overexpression of DDC in the primary tumor was associated with longer OS (p = 0.03). Stimulation with epinephrine induced the downregulation of DDC (p = 0.038) and significantly increased viability in T47D cells (p = 0.028). In contrast, epinephrine induced an upregulation of DDC and decreased the proliferation of MCF7 cells (p = 0.028). Epinephrine led to an upregulation of Gi protein expression in MCF7 cells (p = 0.008). DDC is a positive prognostic factor for OS in breast cancer patients, and it is regulated through epinephrine differently in MCF7 and T47D. DDC may represent a novel target for the treatment of breast cancer, especially concerning its interaction with epinephrine.

• Authors: Eileen Tremmel, Christina Kuhn, Till Kaltofen, Theresa Vilsmaier, Doris Mayr, Sven Mahner, Nina Ditsch, Udo Jeschke, Aurelia Vattai
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 24 (Dec 15 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33334070 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Receptors, G-Protein-Coupled
• Aromatic-L-Amino-Acid Decarboxylases
• DDC protein, human
• Epinephrine

Topics

• Aromatic-L-Amino-Acid Decarboxylases (genetics, metabolism)
• Biomarkers, Tumor
• Breast Neoplasms (metabolism, mortality, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cells, Cultured
• Epinephrine (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Prognosis
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Tumor Burden