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.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1179-1314 |
Language: | English |
Item ID: | 80841 |
Date Deposited: | 15. Dec 2021, 14:55 |
Last Modified: | 15. Dec 2021, 14:55 |