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 (T3), thyronamines, and tetraiodothyroacetic acid (Tetrac) on the expression of TAAR1 in breast cancer cells.
Methods
The effect of T3, 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 (T1AM) significantly increased TAAR1 protein expression (P=0.008). In T47D cells, TAAR1 expression was significantly upregulated after the addition of 10 µg/mL estradiol to 10 nM T1AM (P=0.008). A significant (P=0.028) reduction in MCF-7 cell viability through the incubation with T1AM could be detected. Cell migration of MCF cells was significantly reduced through incubation with 10 nM T1AM.
Conclusion
A significant upregulation of TAAR1 induced by stimulation with T1AM 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 T1AM-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.
Supplementary materials
Figure S1 Real-time TaqMan® PCR in MCF7- and T47D- cells after stimulation with T1AM.
Abbreviation: T1AM, 3-iodothyronamine.
![Figure S1 Real-time TaqMan® PCR in MCF7- and T47D- cells after stimulation with T1AM.](/cms/asset/b011ac7a-4336-480d-b456-2379523eb79f/dbct_a_30858725_f0008_c.gif)
Figure S2 Real-time TaqMan® PCR in MCF7- and T47D- cells after stimulation with Tetrac.
Abbreviation: Tetrac, tetraiodothyroacetic acid.
![Figure S2 Real-time TaqMan® PCR in MCF7- and T47D- cells after stimulation with Tetrac.](/cms/asset/cbcb6bc3-8d5e-4fd7-999a-8156212b4fae/dbct_a_30858725_f0009_c.gif)
Figure S3 Western Blot analysis of TAAR1 protein expression in MCF7 and T47D cells after stimulation with T1AM.
Abbreviation: T1AM, 3-iodothyronamine.
![Figure S3 Western Blot analysis of TAAR1 protein expression in MCF7 and T47D cells after stimulation with T1AM.](/cms/asset/886bbe25-1055-4da1-8455-9a3a1ce3e987/dbct_a_30858725_f0010_c.gif)
Acknowledgments
In memory, we thank Sandra Schulze for her excellent technical assistance in this article. The study was funded by the Bayerische Gleichstellungsförderung grant (2016/2017) of Bavaria, Germany, and by the Foundation of the Frankfurter Allgemeinen Zeitung (FAZIT) foundation grant (2017/2018) of Germany.
Author contributions
AV, UJ, ET, and ND conceived and designed the experiments. ET, CK, and SiH performed the experiments. AV, UJ, ET, CK, SiH, and KH analyzed the data. ET, AV, UJ, and KH wrote the research article. SM, KH, SH, HH, DM, NH, RW, and ND interpreted the results and revised the manuscript. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.