乳腺癌是女性最常见的恶性肿瘤。有研究发现hTERT基因在乳腺癌发生发展中起重要作用。然而,在乳腺癌中如何调控hTERT表达并进而影响端粒酶活性及其在乳腺癌发生发展中的作用及机制，尚不十分明确。前期研究中运用我们设计的新型启动子垂钓鉴定系统已在肺癌细胞中成功垂钓鉴定出hTERT启动子结合蛋白AP-2β，在乳腺癌和肺癌细胞中初步垂钓出CPSF4。在此基础上，我们将：1）在乳腺癌中运用该垂钓鉴定系统进一步垂钓、鉴定新的hTERT启动子结合蛋白；2）研究它们如何调控hTERT启动子活性，进而如何影响细胞转化和肿瘤形成；3）我们还将进一步研究它们在不同类型乳腺癌组织中的表达及作用。通过本课题，旨在进一步阐明乳腺癌中hTERT调控的分子机制，发现部分新的hTERT调控因子，以期发现新的乳腺癌诊断指标及治疗靶点。

Breast cancer is the most common malignancy in women. hTERT gene has been found to play an important role in breast cancer. However, it is unclear how to regulate hTERT gene expression and further affect the activity of telomerase and we still know little about the function and mechanism of hTERT in the development of breast cancer. We have got and identified a hTERT promoter binding protein AP-2β in a lung cancer cell line by our new pulldown assay system and found it can specifically bind to hTERT promoter and promote hTERT expression.So, based on our previous study, we will: 1)further pulldown and identify hTERT promoter binding proteins from breast cancer cell lines by proteomics; 2) investigate how they regulate hTERT promotor activity and how they affect cellular transfomation and oncogenesis; 3) explore their functions and expressions in different breast cancer tissues and evaluate their potential as novel tumor markers or therapeutic targets.