Division of Surgery, School of Medicine, National University of Ireland Galway, Galway, Ireland.
PLoS One. 2011 Jan 19;6(1):e16023. doi: 10.1371/journal.pone.0016023.
The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.
Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression.
The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log(10) Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log(10)RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log(10)RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = 0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold).
Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.
人类乳腺组织中钠碘转运体（NIS）的存在、相关性和调节仍知之甚少。本研究旨在定量分析人乳腺组织中 NIS 和推定调节剂的相对表达，并进一步在体外观察所观察到的关系。
通过针对 NIS、维甲酸受体（RARα、RARβ）、雌激素受体（ERα）、甲状腺激素（THRα、THRβ）和磷酸肌醇-3-激酶（PI3K）的 RQ-PCR 分析人乳腺组织标本（恶性 n=75、正常 n=15、纤维腺瘤 n=10）。用维甲酸（ATRA）、雌二醇和甲状腺素单独以及组合处理乳腺癌细胞，然后分析 NIS 表达的变化。
NIS 的最低水平在正常组织中检测到（Mean(SEM) 0.70(0.12) Log(10)相对数量 (RQ)），在纤维腺瘤（1.69(0.21) Log(10)RQ，p<0.005）和恶性乳腺组织中观察到显著较高的水平（1.18(0.07) Log(10)RQ，p<0.05）。在人 NIS 与 ERα（r = 0.22，p<0.05）和 RARα（r = 0.29，p<0.005）之间观察到显著的正相关，在 NIS 与 RARβ 之间观察到最强的关系（r = 0.38，p<0.0001）。还观察到 NIS 与 PI3K 表达之间的反比关系（r = 0.21，p<0.05）。体外，ATRA、雌二醇和甲状腺素单独刺激 NIS 表达显著增加（范围 6-16 倍），而 ATRA 和甲状腺素联合导致最大增加（范围 16-26 倍）。
尽管 NIS 在恶性乳腺组织中表达明显高于正常乳腺组织，但在纤维腺瘤中检测到最高水平。所提出的数据支持维甲酸和雌二醇在体内乳腺 NIS 调节中的作用，还突出了甲状腺激素对乳腺 NIS 介导的潜在甲状腺调节作用。
