The mammary gland sodium/iodide symporter (mgNIS)

乳腺钠/碘同向转运体 (mgNIS)

• 批准号: 7267218
• 负责人: Nancy Carrasco
• 金额: $ 6.11万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267218
• 关键词: MCF7 cell; SDS polyacrylamide gel electrophoresis; adenocarcinoma; breast neoplasms; cell membrane; fine needle aspiration; flow cytometry; human tissue; immunofluorescence technique; immunoprecipitation; iodine; ion transport; laboratory mouse; lactation; magnetic resonance imaging; mammary gland; membrane transport proteins; metastasis; molecular chaperones; neoplasm /cancer diagnosis; neoplasm /cancer therapy; phosphorylation; polymerase chain reaction; protein transport; sodium ion; western blottings

DESCRIPTION (provided by applicant): The Na symporter (NIS) is a plasma membrane protein that mediates active I- transport in the thyroid and other tissues, including salivary glands, gastric mucosa, and lactating mammary glands (MG). NIS is regulated differently in each tissue. NIS-mediated I- transport in the thyroid is the first step in thyroid hormone biosynthesis. Endogenous functional expression of NIS in thyroid cancer is the foundation for the single most effective and most side effect-free anti-cancerous targeted radiation therapy available, i.e. radioiodide therapy, which has been successfully used in thyroid cancer for over 60 years. Our group isolated the cDNA encoding NIS and generated anti-NIS Abs. We have characterized thyroid NIS and its regulation. Mammary gland NIS (mgNIS) mediates active I- transport in lactating mammary cells, from which I- is passively translocated via a different transporter to the milk. mgNIS is expressed in lactating (but not in non-lactating) MG. mgNIS is regulated by estrogen, prolactin, and oxytocin. Mammary adenocarcinomas in transgenic mice display mgNIS-mediated active I- uptake. The only two cancers in which endogenous functional NIS is expressed are thyroid cancer and breast cancer. Over 80% of human breast cancers express mgNIS, but it is still unknown in what percentage of these NIS is functional. Normal non-lactating human breast samples do not express mgNIS. The endogenous expression of NIS in breast cancer provides an immense advantage over other cancers, into some of which NIS has been ectopically expressed by virus-mediated gene transfer. To characterize mgNIS in mammary cells and ascertain its potential value in breast cancer diagnosis and treatment, we propose: 1. a) To characterize the regulation of mgNIS in mammary cell lines; b) to investigate the effects of systemic and local regulatory factors on the expression of mgNIS in vivo; c) to determine whether low temperature and chemical chaperones promote targeting of mgNIS to the plasma membrane; d) to complement our understanding of I- translocation in the lactating mammary gland by assessing the role of putative apical I- transporters. 2) To develop a radioiodide therapeutic protocol and assess its effectiveness in the treatment of adenocarcinomas in animal models. 3) To ascertain, in fine needle aspirates from both human primary breast tumors and metastases, the functional expression of mgNIS and its possible correlation with other breast cancer parameters.

描述（由申请人提供）：NA Symporter（NIS）是一种质膜蛋白，可介导甲状腺和其他组织中的活性I-转运，包括唾液腺，胃粘膜和乳腺乳腺（MG）。 NIS在每个组织中的调节都不同。甲状腺中的NIS介导的I-转运是甲状腺激素生物合成的第一步。 NIS在甲状腺癌中的内源性功能表达是可用的最有效和最大副作用的抗癌性靶向放射治疗的基础，即放射碘治疗，已成功用于甲状腺癌已有60多年的历史。我们的小组分离了编码NIS的cDNA并产生了抗NIS ABS。我们已经表征了甲状腺NIS及其调节。乳腺NIS（MGNIS）介导了哺乳动物细胞中的主动I-转运，I-从中通过不同的转运蛋白被动地转移到牛奶中。 MGNIS以泌乳（但不在非乳酸）毫克状态表达。 MGNIS受雌激素，催乳素和催产素的调节。转基因小鼠中的乳腺腺癌显示MGNIS介导的活性I-摄取。唯一表达内源性功能性NIS的两种癌症是甲状腺癌和乳腺癌。超过80％的人类乳腺癌表达MGNIS，但在这些NIS中有哪些百分比是功能性的。正常的非泌乳人类乳房样品不表达MGNIS。 NIS在乳腺癌中的内源性表达比其他癌症具有巨大的优势，其中一些NIS已通过病毒介导的基因转移在异位表达。为了表征乳腺细胞中MGNIS并确定其在乳腺癌诊断和治疗中的潜在价值，我们建议：1。a）表征乳细胞系中MGNIS的调节； b）研究系统性和局部调节因素对体内MGNIS表达的影响； c）确定低温和化学伴侣是否会促进MGNIS靶向质膜； d）通过评估推定的顶端I-转运蛋白的作用来补充我们对泌乳乳腺中I易位的理解。 2）制定放射碘治疗方案并评估其在动物模型中腺癌治疗的有效性。 3）确定在细针中从人类原发性乳腺肿瘤和转移酶抽吸时，MGNIS的功能表达及其与其他乳腺癌参数的可能相关性。