The mammary gland sodium/iodide symporter (mgNIS)

乳腺钠/碘同向转运体 (mgNIS)

• 批准号: 7433486
• 负责人: Nancy Carrasco
• 金额: $ 6.3万
• 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/7433486
• 关键词: Active Biological Transport; Adenocarcinoma; Adverse effects; Age; Animal Model; Anions; Apical; Biological Assay; Breast; Breast Adenocarcinoma; Cancer Etiology; Cancer Patient; Cancerous; Cell Line; Cell membrane; Cells; Cessation of life; Characteristics; Chemicals; Complement; Complementary DNA; Diagnostic; Discipline of Nursing; Effectiveness; Epithelial; Estrogens; Fine needle aspiration biopsy; Flow Cytometry; Foundations; Gastric Glands; Gastric mucosa; Gene Transfer; Gene Transfer Techniques; Human; Human Milk; Image; Malignant Neoplasms; Malignant neoplasm of thyroid; Mammary Neoplasms; Mammary gland; Mediating; Membrane Glycoproteins; Membrane Proteins; Metastatic Neoplasm to the Lung; Milk; Molecular Chaperones; Mus; Neoplasm Metastasis; Newborn Infant; Oncogenes; Oxytocin; Post-Translational Protein Processing; Primary Neoplasm; Progesterone Receptors; Prolactin; Property; Protocols documentation; Radiation therapy; Radionuclide Imaging; Regulation; Reporting; Research Personnel; Role; Salivary Glands; Sampling; Sampling Studies; Therapeutic; Thyroid Gland; Thyroid Hormones; Thyroid carcinoma; Tissues; Transgenic Mice; Virus; Woman; base; breast cancer diagnosis; cold temperature; hormone biosynthesis; human SLC5A5 protein; in vivo; malignant breast neoplasm; sodium-iodide symporter; symporter; tool; tumor; uptake

The Na+/I- 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.

Na+/I-同向转运体（NIS）是介导甲状腺中主动I-转运的质膜蛋白， 其他组织，包括唾液腺、胃粘膜和泌乳乳腺（MG）。NIS是 在每个组织中调节不同。NIS介导的甲状腺I-转运是甲状腺功能亢进的第一步。 激素生物合成NIS在甲状腺癌中的内源性功能性表达是甲状腺癌治疗的基础。 单一最有效和最无副作用的抗癌靶向放射治疗，即 放射性碘治疗，已成功用于甲状腺癌超过60年。我们集团 分离编码NIS的cDNA并产生抗NIS Abs。我们已经描述了甲状腺NIS及其 调控乳腺NIS（mgNIS）介导泌乳乳腺细胞中的主动I-转运， I-通过不同的转运体被动地转移到乳汁中。mgNIS在哺乳期表达（但在哺乳期不表达）。 非哺乳期）MG。mgNIS受雌激素、催乳素和催产素调节。乳腺癌 转基因小鼠表现出mgNIS介导的主动I-摄取。仅有的两种癌症 在甲状腺癌和乳腺癌中表达功能性NIS。超过80%的人类乳腺癌 express mgNIS，但仍然不知道这些NIS中有多少百分比是可用的。正常非哺乳期 人乳房样品不表达mgNIS。NIS在乳腺癌中的内源性表达提供了 与其他癌症相比，这是一个巨大的优势，在其中一些癌症中，NIS已经被病毒异位表达- 介导的基因转移表征乳腺细胞中的mgNIS并确定其在乳腺中的潜在价值 癌症的诊断和治疗，我们建议：1。a）表征乳腺细胞中mgNIS的调节 B）研究全身和局部调节因素对MGNIS在细胞中表达的影响。 c）确定低温和化学分子伴侣是否促进mgNIS靶向于 质膜; d）补充我们对哺乳期乳腺中I-易位的理解 通过评估假定的顶端I-转运蛋白的作用。2)制定放射性碘治疗方案， 评估其在动物模型中治疗腺癌的有效性。3)为了确定，最后 从人原发性乳腺肿瘤和转移瘤中针吸物， mgNIS及其与其他乳腺癌参数的可能相关性。