内分泌耐药是雌激素受体阳性（Estrogen Receptor，ER）乳腺癌患者临床治疗效果不佳的关键原因之一。约1/3患者接受一线内分泌药物治疗后会出现复发/转移，而肿瘤细胞干样特性增强是导致内分泌耐药的重要机制之一，但是很多关键机制尚不清楚。我们近期首次报道了炎性-干性相关分子PDE3A与乳腺癌关系密切，前期结果显示ER阳性乳腺癌中PDE3A表达显著上调并通过富集肿瘤干细胞和维持干性使乳腺癌细胞对内分泌药物治疗敏感性降低，介导继发性耐药；而ER通过配体依赖模式显著促进癌细胞表达PDE3A，属于原发性耐药。基于此，我们设想PDE3A过表达与乳腺癌干细胞样表征相关，是导致乳腺癌内分泌耐药的重要因素，可能在肿瘤治疗中有重要作用。我们拟以ER阳性乳腺癌为研究对象，通过临床资料和细胞分子生物学技术，体内外实验阐明PDE3A介导乳腺癌内分泌耐药的作用及分子机制，为乳腺癌靶向内分泌治疗提供理论基础。

Endocrine resistance is one of the key factors for the poor therapeutic effect of Estrogen Receptor (ER) positive breast cancer. About 1/3 of patients treated with first-line endocrine therapies run the risk of metastasis or relapse, and cancer stem cells (CSC) are one of the important mechanisms leading to endocrine resistance. However, many of the key mechanisms remain unclear. We recently reported the inflammatory-stemness associated gene PDE3A is closely related to breast cancer. And the preliminary data showed that the expression of PDE3A in ER positive breast cancer subtype was significantly up-regulated, which reduced the sensitivity of breast cancer cells to endocrine therapy through enrichment and maintenance of cancer stem cells, which was acquired resistance. In addition, ER significantly promoted the expression of PDE3A in breast cancer cells via ligand-dependent mode, which was de novo resistance. Thus, we hypothesized that the overexpression of PDE3A is related to the stem-cell like property in breast cancer, which is an important factor leading to endocrine resistance of breast cancer and may play an important role in endocrine therapy. We will analyze clinical data and clarify the role and molecular mechanism of endocrine resistance mediated by PDE3A in breast cancer through molecular biology technology in vivo and in vitro, so as to provide theoretical basis for targeted endocrine therapy of breast cancer.