催产素受体OXTR激活Prolactin通路促进乳腺癌发生的机制研究

乳腺癌是全球女性中发病率最高的恶性肿瘤。催产素受体(Oxytocin Receptor，OXTR)是一个含7个跨膜结构域的G蛋白偶联受体，主要功能是参与母性行为、社交行为、能量代谢、体温调节和泌乳。OXTR在人的乳腺肿瘤和乳腺癌细胞系中均有表达；但OXTR是否调节乳腺癌发生进程，具体调节机理尚不清楚。我们发现，过表达Oxtr诱导了HER2阳性乳腺肿瘤的发生，激活Prolactin/p-STAT5通路；而将此通路抑制后，便缓解了OXTR诱导的乳腺癌发生进程。我们推测：OXTR通过Prolactin/p-STAT5通路调节乳腺癌的发生发展。本项目拟在动物和细胞水平过表达/敲除Oxtr，进行乳腺癌进程、增殖和迁移的研究，探索OXTR调节乳腺癌的发生机理，意在揭示OXTR新的生物学功能，为乳腺癌的诊断和治疗提供新思路和新靶点。

Breast cancer is a malignant tumor with the highest morbidity among women worldwide. Oxytocin Receptor (OXTR) is a G protein-coupled receptor with 7 transmembrane domains, known to be involved in maternal behavior, social behavior, energy metabolism, thermoregulation and milk yield. OXTR expression has been detected in breast cancer and breast cancer cell lines, suggesting its possible involvement in breast cancer. However, its roles and regulatory mechanism in mammary tumorigenesis have not been reported. Our study shows OXTR overexpression induces HER2+ mammary tumors in ++Oxtr females, and increases prolactin-induced STAT5 activation. Prolactin inhibitor bromocriptine mitigates OXTR-driven hyper-mammogenesis and mammary tumor growth. This suggests OXTR may induce mammary tumorigenesis through prolactin/p-STAT5 pathway. We intends to explore the roles of Oxtr in breast cancer through mutation of Oxtr in transgenic mice and cell lines for revealing the new function of Oxtr, which provides new ideas for clinical diagnosis and treatment of breast cancer.