Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
Department of Obstetrics and Gynaecology, University Hospital Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany.
Int J Mol Sci. 2020 Dec 15;21(24):9565. doi: 10.3390/ijms21249565.
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 ( = 0.03). Stimulation with epinephrine induced the downregulation of DDC ( = 0.038) and significantly increased viability in T47D cells ( = 0.028). In contrast, epinephrine induced an upregulation of DDC and decreased the proliferation of MCF7 cells ( = 0.028). Epinephrine led to an upregulation of Gi protein expression in MCF7 cells ( = 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.
甲状腺功能障碍与乳腺癌发病率之间存在一致性。甲状腺激素代谢物与 TAAR1(微量胺相关受体 1)结合,并通过这种方式调节 5-羟色胺能和多巴胺能系统。儿茶酚胺本身是由 L-多巴脱羧酶(DDC)合成的。我们的研究目的是分析儿茶酚胺对原发性乳腺癌患者 DDC 表达的影响,以及 DDC 与总生存期(OS)的关系。通过免疫组织化学分析 DDC 表达。通过 Western blot 分析肾上腺素对 DDC 和 Gi 蛋白表达的影响。进行活力测定以测试代谢细胞活力。原发肿瘤中 DDC 的过表达与更长的 OS 相关( = 0.03)。肾上腺素的刺激诱导 DDC 的下调( = 0.038),并显著增加 T47D 细胞的活力( = 0.028)。相比之下,肾上腺素诱导 MCF7 细胞中 DDC 的上调并降低增殖( = 0.028)。肾上腺素导致 MCF7 细胞中 Gi 蛋白表达的上调( = 0.008)。DDC 是乳腺癌患者 OS 的一个正预后因素,并且在 MCF7 和 T47D 中通过肾上腺素以不同的方式调节。DDC 可能代表治疗乳腺癌的一个新靶点,特别是考虑到其与肾上腺素的相互作用。