基质细胞p85突变在乳腺肿瘤血管生成中的作用研究

乳腺癌是严重威胁女性健康和生命安全的恶性肿瘤，但其分子病理机制至今仍不十分清楚。癌组织中不同细胞间的信号通讯对肿瘤的发生发展近期受到人们高度关注。PI3K是细胞内众多信号转导网络中心的重要激酶，研究发现约30%的乳腺癌病人PI3K 基因发生突变，这种突变对乳腺癌的发生发展有何意义很不明确。本项目将围绕肿瘤组织细胞之间相互关系，研究基质成纤维细胞PI3K激酶的p85α亚基突变在乳腺肿瘤血管生成中的作用。前期初步研究结果发现，p85α突变的成纤维细胞条件培养基（CM）可显著促进血管内皮细胞HUVEC增殖及血管环的形成，后续研究将在现有基础上，通过体外和体内实验，确定基质成纤维细胞p85α突变促进血管内皮细胞增殖和转移的信号分子，并阐明其作用机理和信号转导途径。研究结果将为理解基质细胞基因突变对乳腺癌发生发展的意义、发展针对特定靶点的治疗方法和早期基因诊断手段提供可行的实验方法和理论依据。

Breast cancer is one of the serious diseases all over the world and it is largely harmful for the health of female patients in our country. However, the molecular mechanism of breast cancer is still not fully understood. There are evidences that the signaling communication between breast stromal-endothelial interactions play a role in breast cancer development. PI3K pathway is the center point of the various cells signaling network. Clinical statistics indicates there are about 30% patients who have breast cancer with a mutation of their PI3K gene, especially its subunit p85α. However, the meaning of this mutation for the tumor angiogenesis and development is still unknown. This study will focus on the relations of stromal-endothelial interaction, investigate the role of the breast stromal cells p85α mutation on effects of the angiogenesis of the edothelail cells. In previous studies, we have found that condition medium of MEF (murine embryonic fibroblasts) p85α mutated significantly promoted the proliferation and angiogenesis of endothelial cell HUVEC and EOMA. In the following study, we will detect the signal molecule between the stromal-endothelial interaction through in vivo and in vitro experiments to reveal the mechanism and signaling pathway. The result of this study will boost the understanding of gene mutations' effect on tumor angiogenesis of breast cancer as well as develop a potential alternative of novel targeting therapies and gene diagnosis techniques.