VIDEO IMAGING OF CALCIUM AND PH IN BREAST CANCER CELLS

乳腺癌细胞中钙和 PH 的视频成像

• 批准号: 6131162
• 负责人: IGOR N SERGEEV
• 金额: $ 2.74万
• 依托单位: SOUTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6131162
• 关键词: 1,25 dihydroxycholecalciferol; acidity /alkalinity; breast neoplasms; buffers; calcium channel; calcium flux; calcium indicator; cell growth regulation; digital imaging; fluorescence microscopy; growth inhibitors; hormone regulation /control mechanism; intracellular transport; neoplastic growth; tissue /cell culture; video microscopy; vitamin D receptors; vitamin analog

DESCRIPTION (Adapted from the Applicant's Abstract): Intracellular free calcium and intracellular pH play a critical role in cell proliferation, differentiation and death. The Ca+ regulating hormone 1,25(OH)2-vitamin D3 (1,25(OH)2D3) inhibits proliferation of breast cancer cells, but its therapeutic potential is limited by hypercalcemia. The antiproliferative activity of 1,25(OH)2D3 analogues (deltanoids) does not depend significantly on vitamin D receptors (VDR) present in breast cancer cells. Nongenomic effects of 1,25(OH)2D3, particularly on calcium and pH, may determine, to a substantial extent, its role in cellular homeostasis. The authors have shown that several analogs induce non- genomic versus genomic effects, and that 1,25(OH)2D3 regulates calcium entry into the cell through voltage-insensitive calcium channels (VICC) coupled to plasmalemmal VDR, and mobilizes the ryandone-sensitive endoplasmic reticulum calcium stores. The purpose of this project is to determine the mechanism by which 1,25(OH)2D3 exerts its antiproliferative effects. This will be done by testing whether the D3 analog-agonists increase Ca+ influx, causing apoptosis, or whether analog-antagonists inhibit calcium entry and suppress cell proliferation. Comparison of these effects, along with prodifferentiating activities of the analogs versus binding to VDR, the ability of the analogs to activate VICC and mobilize calcium stores, will help in understanding the roles of D3 and calcium in breast cancer, and will be useful in designing new anticancer d3 analogs.

描述（改编自申请人的摘要）：细胞内游离 钙和细胞内 pH 在细胞增殖中起着至关重要的作用， 分化和死亡。 Ca+ 调节激素 1,25(OH)2-维生素 D3 (1,25(OH)2D3) 抑制乳腺癌细胞增殖，但其 治疗潜力受到高钙血症的限制。抗增殖剂 1,25(OH)2D3 类似物（deltanoids）的活性不依赖于 对乳腺癌中存在的维生素 D 受体 (VDR) 具有显着影响 细胞。 1,25(OH)2D3 的非基因组效应，特别是对钙和 pH 值可能在很大程度上决定其在细胞中的作用 体内平衡。作者已经表明，几种类似物会诱导非 基因组与基因组效应，以及 1,25(OH)2D3 调节钙 通过电压不敏感钙通道 (VICC) 进入细胞 与质膜 VDR 耦合，并动员对 ryandone 敏感的 内质网钙储存。该项目的目的是 确定 1,25(OH)2D3 发挥抗增殖作用的机制 影响。这将通过测试 D3 类似物激动剂是否 增加 Ca+ 流入，导致细胞凋亡，或者类似物拮抗剂 抑制钙的进入并抑制细胞增殖。 比较 这些效应以及类似物的促分化活性 与结合 VDR 相比，类似物激活 VICC 的能力和 调动钙储备，将有助于理解 D3 和 乳腺癌中的钙，将有助于设计新的抗癌药物 d3 类似物。