Tremmel Eileen, Hofmann Simone, Kuhn Christina, Heidegger Helene, Heublein Sabine, Hermelink Kerstin, Wuerstlein Rachel, Harbeck Nadia, Mayr Doris, Mahner Sven, Ditsch Nina, Jeschke Udo, Vattai Aurelia
Breast Center, Department of Gynecology and Obstetrics and CCC Munich, University of Munich (LMU), 81377 Munich, Germany,
Department of Gynecology and Obstetrics, University of Heidelberg, 69120 Heidelberg, Germany.
Breast Cancer (Dove Med Press). 2019 Feb 19;11:87-97. doi: 10.2147/BCTT.S178721. eCollection 2019.
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), thyronamines, and tetraiodothyroacetic acid (Tetrac) on the expression of TAAR1 in breast cancer cells.
The effect of T, 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.
Stimulation of MCF-7 cells with 10 nM 3-iodothyronamine (TAM) significantly increased TAAR1 protein expression (=0.008). In T47D cells, TAAR1 expression was significantly upregulated after the addition of 10 µg/mL estradiol to 10 nM TAM (=0.008). A significant (=0.028) reduction in MCF-7 cell viability through the incubation with TAM could be detected. Cell migration of MCF cells was significantly reduced through incubation with 10 nM TAM.
A significant upregulation of TAAR1 induced by stimulation with TAM 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 TAM-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.
乳腺癌与甲状腺疾病之间存在相关性，这在老年女性中很常见。甲状腺激素会降解为痕量胺，痕量胺可与G蛋白偶联受体痕量胺相关受体1（TAAR1）结合并激活它。甲状腺激素向痕量胺的转化由鸟氨酸脱羧酶完成。此前，我们发现在长达14年的长期随访中，TAAR1过表达（免疫反应评分≥6）与原发性乳腺癌患者显著更长的总生存期相关。本研究的目的是分析TAAR1在乳腺癌细胞系中的调控情况，以及三碘甲状腺原氨酸（T3）、甲状腺胺和四碘甲状腺乙酸（Tetrac）对乳腺癌细胞中TAAR1表达的影响。
通过聚合酶链反应（PCR）和蛋白质免疫印迹法（Western blot）分析T3、甲状腺胺和Tetrac对乳腺癌细胞系MCF-7和T47D中TAAR1表达的影响。进行MTT试验以检测细胞代谢活力。进行划痕试验以分析细胞迁移情况。
用10 nM 3-碘甲状腺胺（TAM）刺激MCF-7细胞可显著增加TAAR1蛋白表达（P = 0.008）。在T47D细胞中，向10 nM TAM中添加10 μg/mL雌二醇后，TAAR1表达显著上调（P = 0.008）。通过与TAM孵育可检测到MCF-7细胞活力显著降低（P = 0.028）。用10 nM TAM孵育可显著降低MCF细胞的迁移能力。
TAM刺激诱导的TAAR1显著上调可能表明乳腺癌细胞中甲状腺激素脱羧作用增强。此外，雌二醇似乎对T47D细胞中TAM诱导的TAAR1上调有影响。TAAR1相关的细胞转导机制似乎是乳腺癌患者内分泌治疗选择的一个有趣靶点。
