FOXC1对基底样型乳腺癌侵袭性生物学行为的影响及相关分子机制的研究

项目名称： FOXC1对基底样型乳腺癌侵袭性生物学行为的影响及相关分子机制的研究

项目编号： No.81202083

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： 喻林

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 基底样型乳腺癌(BLBC)具有高度侵袭性的生物学行为，预后较差。我们前期基因芯片的结果提示，BLBC高表达FOXC1，并与预后差有相关性。迄今对FOXC1与BLBC生物学行为的关系及相关机制仍知之甚少。FOXC1如何影响BLBC侵袭性的生物学行（增殖、迁移、侵袭转移），起促进还是抑制作用？相关分子机制如何？BRCA1是否与c-myc相互作用，调控FOXC1的表达？为回答这些科学问题，我们将通过BLBC细胞系、动物移植瘤模型、乳腺癌组织，采用Real-time PCR、Western blot、RNA干扰、染色质免疫沉淀等手段，从分子、细胞、组织及动物整体水平等多方面探讨FOXC1在BLBC发生发展中的作用。明确FOXC1对BLBC侵袭性生物行为的影响及机制，初步阐明FOXC1过表达的可能分子途径。本项目将从FOXC1这个新视点为揭示BLBC预后差的分子机制奠定基础，并为其治疗提供新思路。

中文关键词： 三阴性乳腺癌；基底样型乳腺癌；FOXC1；生物学行为；分子机制

英文摘要： Basal-like breast cancer（BLBC）has highly aggressive biological behavior and poor prognosis. Our previous study by cDNA microarray indicated that BLBC showed overexpression of the transcription factor FOXC1 which was associated with poor prognosis of BLBC. So far, there has been very few knowledge about the relation and implicated mechanisms underlying FOXC1 expression and the biological behavior of BLBC. How does FOXC1 impact aggressive biological behavior ( proliferation, migration, invasion/metastasis) of BLBC? Promotion or inhibition of proliferation, migration, invasion/metastasis of BLBC? what is implicated mechanisms? Is FOXC1 regulated by the interaction of BRCA1 and c-myc? In order to explain these scientific questions, using three experimental models -establised basal-like breast carcinoma cell lines, xenograft in nude mouse mammary pad, and human breast cancer tissues -this project will explore the important role of FOXC1 in the pathogenesis and development of BLBC from molecule, cell line, tissue and animal levels, by varied methods of Real-time PCR, Western blot,Chromatin immunoprecipitation , RNA interference and so on. Our aims is to clarify the impacts and implicted mechanisms of FOXC1 in the proliferation, migration, invasion/metastasis of BLBC, initially elucidate the regulation mechanisms of FO

英文关键词： triple negative breast cancer；basal-like breast cancer；FOXC1；biological behaviour；molecular mechanism