HOXD3通过驱动乳腺癌细胞干细胞样特性在化疗耐药中的作用机制研究

HOXD3, a member of Hox gene family, is responsible for tumor invasion and metastasis in several cancers. However, the function of HOXD3 in chemo-resistance is still unknown. In previous study，we demonstrated that HOXD3 positive expression was a significant unfavorable prognostic factor for patients with breast cancer. Recently, we found that HOXD3-positive breast cancer cells had the properties of breast cancer stem cells. Furthermore, HOXD3 activated several chemo-resistance pathways, and played an important role in chemo-resistance of breast cancer cells. Thus we proposed that HOXD3 might drive stem-like properties of breast cancer cells that promote breast cancer initiation, development and drug resistance. In the current study, by experiments in vitro and in vivo, we will explore the stem-like properties of HOXD3 positive breast cancer cells. Using siRNA, plasmid transfection, gene microarray and co-immunoprecipitation, we will discuss the function of HOXD3 in regulating the malignant biological behaviors of breast cancer cells. We will also study the mechanism of drug resistance mediated by HOXD3. This study will be contributed to understanding the biological characteristics of breast cancer, and providing theoretical basis for prognosis and treatment selection for patients with breast cancer.

HOXD3属同源异形盒基因家族成员，在多种恶性肿瘤的侵袭、转移过程中发挥重要作用。但HOXD3在化疗耐药中的作用尚未明确。我们已证实HOXD3高表达是乳腺癌预后不良的独立危险因素。近期研究中我们发现：HOXD3阳性乳腺癌细胞具有乳腺癌干细胞样特性；HOXD3可活化多条化疗耐药通路，HOXD3在乳腺癌细胞化疗耐药过程中发挥重要作用。综上，我们提出科学假说：HOXD3作为乳腺癌干细胞分子标志物，驱动乳腺癌细胞获得干细胞样特性，影响乳腺癌的发生、发展，并参与化疗耐药过程。本研究将以乳腺癌细胞、裸鼠移植瘤及乳腺癌组织为研究对象，运用基因敲除、质粒转染、免疫共沉淀、基因芯片等方法，明确HOXD3阳性乳腺癌细胞的干细胞样特性，探讨HOXD3表达对化疗耐药的影响并研究其调控机制。本研究的结果有助于更好地认识乳腺癌细胞的生物学特性，为乳腺癌患者预后评估及治疗选择提供理论依据。

HOXD3属同源异形盒基因家族成员，在多种恶性肿瘤的侵袭、转移过程中发挥重要作用。但HOXD3在化疗耐药中的作用尚未明确。我们已证实HOXD3高表达是乳腺癌预后不良的独立危险因素。近期研究中我们发现：HOXD3阳性乳腺癌细胞具有乳腺癌干细胞样特性；HOXD3可活化多条化疗耐药通路，HOXD3在乳腺癌细胞化疗耐药过程中发挥重要作用。本研究中我们证实：HOXD3作为乳腺癌干细胞分子标志物，驱动乳腺癌细胞获得干细胞样特性，影响乳腺癌的发生、发展，并参与化疗耐药过程。本研究以乳腺癌细胞、裸鼠移植瘤及乳腺癌组织为研究对象，运用基因敲除、质粒转染、免疫共沉淀、基因芯片等方法，明确HOXD3阳性乳腺癌细胞的干细胞样特性，探讨HOXD3表达对化疗耐药的影响并研究其调控机制。本研究的结果有助于更好地认识乳腺癌细胞的生物学特性，为乳腺癌患者预后评估及治疗选择提供理论依据。