Arczewska Katarzyna D, Godlewska Marlena, Krasuska Wanda, Łyczkowska Anna, Kiedrowski Mirosław, Czarnocka Barbara
Department of Biochemistry and Molecular Biology, Center of Postgraduate Medical Education, Warsaw, Poland.
Arch Med Sci. 2019 Nov 25;18(4):1041-1050. doi: 10.5114/aoms.2019.89980. eCollection 2022.
Thyroid iodide transporters, Na/I symporter (NIS) and pendrin (PDS), are responsible for supplying this vital micronutrient for thyroid hormone synthesis by thyroid peroxidase (TPO). Both proteins were shown to be expressed, apart from the thyroid, also in other human tissues, including lactating mammary gland. NIS expression in human breast cancers has been widely studied. On the other hand, until now mRNA levels in breast tumor tissue have been estimated only in high throughput analyses. Previously, we have observed that TPO is expressed in normal and cancerous human breast tissues and shows enzymatic activity. However, biochemical activity of TPO in human breast cancer cells requires iodide transport by NIS and PDS. Therefore, to extend our previous study on TPO expression and function in human breast tumors we performed analysis of NIS and PDS levels in the same group of patients.
The study involved detection of NIS and PDS protein levels by immunohistochemistry and Western blotting, as well as mRNA levels by real-time quantitative polymerase chain reaction.
Here we provide direct evidence that NIS and PDS are expressed in human breast cancer tissue, with NIS levels being increased and PDS levels decreased in tumor tissue. Interestingly, mRNA levels in breast cancer tissue seem to be influenced by the estrogen receptor status and age of the patients, while mRNA levels were dependent on histological type of the tumor.
This study provides valuable information important for consideration in diagnostic or therapeutic application of radioiodine in breast cancer management.
甲状腺碘转运体，钠/碘同向转运体（NIS）和pendrin（PDS），负责为甲状腺过氧化物酶（TPO）合成甲状腺激素提供这种重要的微量营养素。已证明这两种蛋白除了在甲状腺中表达外，在包括哺乳期乳腺在内的其他人体组织中也有表达。NIS在人类乳腺癌中的表达已得到广泛研究。另一方面，到目前为止，仅在高通量分析中估计了乳腺肿瘤组织中的mRNA水平。此前，我们观察到TPO在正常和癌性人类乳腺组织中表达并显示出酶活性。然而，人类乳腺癌细胞中TPO的生化活性需要NIS和PDS进行碘转运。因此，为了扩展我们之前关于TPO在人类乳腺肿瘤中表达和功能的研究，我们对同一组患者的NIS和PDS水平进行了分析。
该研究包括通过免疫组织化学和蛋白质印迹法检测NIS和PDS蛋白水平，以及通过实时定量聚合酶链反应检测mRNA水平。
在这里，我们提供了直接证据，证明NIS和PDS在人类乳腺癌组织中表达，肿瘤组织中NIS水平升高而PDS水平降低。有趣的是，乳腺癌组织中的mRNA水平似乎受雌激素受体状态和患者年龄的影响，而mRNA水平则取决于肿瘤的组织学类型。
本研究提供了有价值的信息，对于在乳腺癌管理中放射性碘的诊断或治疗应用的考虑具有重要意义。
