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碘化钠同向转运体(NIS)在人乳腺癌组织中的功能性表达。

Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue.

作者信息

Upadhyay Geeta, Singh Rajesh, Agarwal Gaurav, Mishra Saroj K, Pal Lily, Pradhan Prasanta K, Das Birendra K, Godbole Madan M

机构信息

Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

出版信息

Breast Cancer Res Treat. 2003 Jan;77(2):157-65. doi: 10.1023/a:1021321409159.

Abstract

Sodium iodide symporter (NIS) is a molecule involved in active accumulation of iodine in thyroid gland for the biosynthesis of thyroid hormone. Its expression has also been demonstrated in extra-thyroidal tissues including lactating mice mammary gland and also in human breast cancers. Iodide transport in thyroid cells through NIS is the basis for using radioiodine for diagnosis and treatment of differentiated thyroid carcinoma. The similar approach may prove beneficial for the diagnosis and treatment of breast cancer if iodine uptake, its retention and NIS expression can be shown unequivocally in malignant tumors. The aim of the present study was to investigate NIS expression, in vivo iodine transport ability and fate of iodine in human breast tumors. Women (age 33-58 years) with infiltrating duct carcinoma confirmed by FNAC and subsequent histopathology were the subject of this study. Expression of NIS RNA and protein was confirmed by RNAase protection assay, western blot and immunohistochemistry respectively in surgically excised breast tumor tissue. Iodine transport ability and its nature was assessed both in vivo and in vitro. We report high NIS expression at both transcriptional and translational level and its ability to transport iodine in human breast tumors. The in vivo iodine transport ability was confirmed by scintigraphy. Unlike thyroid, perchlorate and thiocyanate do not inhibit iodine transport in breast tumors. The presence of iodinated proteins suggests the longer retention time. The unequivocal demonstration of NIS expression, its functionality and retention of iodine by organification further provides supportive evidence for use of radioiodine as an additional treatment modality of human breast carcinoma.

摘要

碘化钠同向转运体(NIS)是一种参与碘在甲状腺中主动积累以合成甲状腺激素的分子。其表达也已在包括哺乳期小鼠乳腺在内的甲状腺外组织以及人类乳腺癌中得到证实。通过NIS在甲状腺细胞中进行碘转运是使用放射性碘诊断和治疗分化型甲状腺癌的基础。如果能在恶性肿瘤中明确显示碘摄取、其滞留情况以及NIS表达,那么类似的方法可能对乳腺癌的诊断和治疗有益。本研究的目的是调查人类乳腺肿瘤中NIS的表达、体内碘转运能力以及碘的去向。经细针穿刺抽吸活检(FNAC)及后续组织病理学确诊为浸润性导管癌的33 - 58岁女性是本研究的对象。分别通过核糖核酸酶保护分析、蛋白质印迹法和免疫组织化学在手术切除的乳腺肿瘤组织中证实了NIS RNA和蛋白质的表达。在体内和体外评估了碘转运能力及其性质。我们报告了人类乳腺肿瘤中NIS在转录和翻译水平上的高表达及其转运碘的能力。通过闪烁扫描术证实了体内碘转运能力。与甲状腺不同,高氯酸盐和硫氰酸盐不会抑制乳腺肿瘤中的碘转运。碘化蛋白的存在表明碘的滞留时间更长。NIS表达、其功能以及通过有机化作用对碘的滞留的明确证明进一步为使用放射性碘作为人类乳腺癌的一种额外治疗方式提供了支持性证据。

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