The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.
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DOI:
10.1371/journal.pone.0016023
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发表时间:
2011-01-19
期刊:
影响因子:
3.7
通讯作者:
Dwyer RM
Dwyer RM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ryan J;Curran CE;Hennessy E;Newell J;Morris JC;Kerin MJ;Dwyer RM

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钠碘转运体(NIS)在人乳腺组织中的存在、相关性和调控仍知之甚少。这项研究的目的是量化NIS和可能的调节因子在人类乳腺组织中的相对表达,并在体外进一步研究它们之间的关系。对人乳腺组织标本(恶性n = 75例,正常n = 15例,纤维腺瘤n = 10例)进行了针对NIS、视黄酸受体(RARα、RARβ)、雌激素(ERα)、甲状腺激素(Thrα、Thrβ)以及磷脂酰肌醇-3-激酶(PI3K)的荧光定量聚合酶链式反应分析。用维甲酸(ATRA)、雌二醇和甲状腺素单独及联合处理乳腺癌细胞,分析NIS表达的变化。NIS在正常乳腺组织中的表达水平最低(平均为0.70log10相对量),而纤维腺瘤组织(1.69Log10RQ,P<0.005)和恶性乳腺组织(1.18Log10RQ,P<0.05)的表达水平显著高于正常乳腺组织。人类NIS与ERα(r = 0.22,p<0.005)和RARα(r = 0.29,p&t;0.005)呈显著正相关,其中与RARβ(r = 0.38,p<0.0001)的相关性最强。NIS与PI3K表达呈负相关(r = −0.21,p<0.05)。在体外,ATRA、雌二醇和甲状旁腺素单独刺激NIS表达显著增加(6-16倍),ATRA和甲状旁腺素联合作用最大(16-26倍)。尽管NIS在恶性乳腺组织中的表达明显高于正常乳腺组织,但在纤维腺瘤中的表达水平最高。这些数据支持维甲酸和雌二醇在体内调节乳房NIS中的作用,也强调了甲状腺激素介导的乳房NIS潜在的甲状腺调节。
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) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, 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.
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发表时间: 2009-04-15
期刊: Cancer research
影响因子: 11.2
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DOI: 10.1210/jc.2004-0907
发表时间: 2004-10-01
影响因子: 5.8
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Knostman, KAB;Cho, JY;Jhiang, SM
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DOI: 10.1210/en.140.11.5422
发表时间: 1999-11-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
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Suzuki, K;Mori, A;Kohn, LD
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DOI: 10.1016/j.bbrc.2006.08.170
发表时间: 2006-11-03
影响因子: 3.1
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Berger, F.;Unterholzner, S.;Spitzweg, C.
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DOI: 10.1023/a:1021321409159
发表时间: 2003-01-01
影响因子: 3.8
作者:
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通讯作者: Godbole, MM