Thyronamine regulation of TAAR1 expression in breast cancer cells and investigation of its influence on viability and migration

Tremmel, Eileen; Hofmann, Simone; Kuhn, Christina; Heidegger, Helene; Heublein, Sabine; Hermelink, Kerstin; Wuerstlein, Rachel; Harbeck, Nadia; Mayr, Doris; Mahner, Sven; Ditsch, Nina; Jeschke, Udo und Vattai, Aurelia (2019): Thyronamine regulation of TAAR1 expression in breast cancer cells and investigation of its influence on viability and migration. In: Breast Cancer-Targets and Therapy, Bd. 11: S. 87-97

Abstract

Objectives: A correlation exists between breast cancer and thyroid disorders, which are common in elderly women. Thyroid hormones are degraded into trace amines, which can bind to the G-protein-coupled receptor trace amine-associated receptor 1 (TAAR1) and thereby activate it. The transformation of thyroid hormones into trace amines is carried out by the ornithine decarboxylase. Previously, we showed that TAAR1 overexpression (IRS >= 6) was associated with a significantly longer OS in primary breast cancer patients during a long-term follow-up of up to 14 years. Aim of the present study was to analyze the regulation of TAAR1 in breast cancer cell lines and the influence of triiodothyronine (T-3), thyronamines, and tetraiodothyroacetic acid (Tetrac) on the expression of TAAR1 in breast cancer cells. Methods: The effect of T-3, thyronamines, and Tetrac on the expression of TAAR1 in breast cancer cell lines MCF-7 and T47D was analyzed via PCR and Western blot. A MTT assay was performed to test the metabolic cell viability. A scratch assay was performed to analyze cell migration. Results: Stimulation of MCF-7 cells with 10 nM 3-iodothyronamine (T(1)AM) significantly increased TAAR1 protein expression (P=0.008). In T47D cells, TAAR1 expression was significantly upregulated after the addition of 10 mu g/mL estradiol to 10 nM T(1)AM (P=0.008). A significant (P=0.028) reduction in MCF-7 cell viability through the incubation with T(1)AM could be detected. Cell migration of MCF cells was significantly reduced through incubation with 10 nM T(1)AM. Conclusion: A significant upregulation of TAAR1 induced by stimulation with T(1)AM may be a sign for an increased decarboxylation of thyroid hormones in breast cancer cells. In addition, there seems to be an influence of estradiol for the T(1)AM-induced upregulation of TAAR1 in T47D cells. TAAR1-related cell transduction mechanisms seem to be an interesting target for endocrine treatment options of breast cancer patients.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1179-1314
• Sprache: Englisch