基于人源性异种移植小鼠模型的乳腺癌骨转移机制研究

项目名称： 基于人源性异种移植小鼠模型的乳腺癌骨转移机制研究

项目编号： No.81202077

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 夏添松

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 乳腺癌骨转移严重危害女性生命和生活质量，其临床治疗和机制研究有待进一步完善。针对难以获取临床骨转移标本的困境，我们在前期工作中构建了新型的人源性乳腺癌骨转移小鼠模型，保证了其原发灶、转移灶和乳腺癌细胞均为人源性。基于该模型，我们获得了匹配的乳腺癌原发灶和骨转移灶标本，并进行了乳腺癌细胞原代培养和提纯，得到了基因组和miRNA组的数据。本研究拟基于该数据对乳腺癌骨转移机制进行深入研究。通过科学甄选，MMP2和SPARC基因成为研究对象。项目通过siRNA干涉和慢病毒转染等基因操作，从细胞生物学行为、动物模型验证、临床标本检测和患者预后研究四个层次阐明候选基因在乳腺癌骨转移过程中的功能。通过软件计算和文献检索，探索它们的上游调控miRNA的作用以及SPARC对MMP2潜在的调节作用。同时以这些研究为基础，继续发掘前期高通量对比研究获得的数据。本研究将加深人们对乳腺癌骨转移的机制的理解。

中文关键词： 金属基质蛋白酶2；MiR-106b；乳腺癌；骨转移；

英文摘要： Bone metastasis of breast cancer seriously harm to female life. But the clinical treatment and mechanistic study still need to be further improved. To solve the difficulty to obtain clinical metastatic bone specimens of breast cancer, we established a novel human-derived bone metastasis mouse model of breast cancer, in which the primary tumor, bone metastasis and breast cancer cells are all human-derived. Based on this model, we obtained the matching specimens of orthotopic breast cancer and bone metastasis. Then we had these breast cancer cells primary cultured and purified, and finally obtained the genome and miRNA data. Based on these data, we will study the mechanisms of breast cancer bone metastasis. MMP2 and SPARC genes were chosen as targets by scientific selection. Using technology of siRNA interference and lentiviral transfection, the effects of the two genes on bone metastasis of breast cancer will be studied in cell biology behavior, animal model validation, clinical specimen's validation and prognosis of patients. Based on software and literature search, their upstream regulatory miRNA and the potential moderating role of SPARC on MMP2 will be discussed. Otherwise, we will continue to analyze the data acquired from the precious high throughput comparative study. This study will deepen the understandi

英文关键词： MMP2；MiR-106b；Breast cancer；bone metastasis；