A Novel Mechanism of hPRL-G129R, a Prolactin Antagonist, Inhibits Human Breast Cancer Cell Proliferation and Migration

文献类型： 外文期刊

第一作者： Li, Ruonan

作者： Li, Ruonan;Yang, Yu;Wang, Yuesi;Ge, Zihan;Liu, Xingjie;Zhou, Yixuan;Zhang, Wei;Xian, Li;Yang, Yu;Lan, Hainan;Yuan, Hongxuan

作者机构：

关键词： breast cancer; PRLR; hPRL-G129R; dual functions antagonist; nuclear localization

期刊名称：ENDOCRINOLOGY （ 影响因子：4.8； 五年影响因子：4.8 ）

ISSN： 0013-7227

年卷期： 2023 年 164 卷 12 期

页码：

收录情况： SCI

摘要： Prolactin (PRL) and its receptor, PRLR, are closely related to the occurrence and development of breast cancer. hPRL-G129R, an hPRLR antagonist, has been found to induce apoptosis in breast cancer cells via mechanisms currently unknown. Recent studies have indicated that PRLR exhibits dual functions based on its membrane/nucleus localization. In that context, we speculated whether hPRL-G129R is a dual-function antagonist. We studied the internalization of the hPRLR-G129R/PRLR complex using indirect immunofluorescence and Western blot assays. We found that hPRL-G129R not only inhibited PRLR-mediated intracellular signaling at the plasma membrane, but also blocked nuclear localization of the receptor in T-47D and MCF-7 cells in a time-dependent manner. Clone formation and transwell migration assays showed that hPRL-G129R inhibited PRL-driven proliferation and migration of tumor cells in vitro. Further, we found that increasing concentrations of hPRL-G129R inhibited the nuclear localization of PRLR and the levels of signal transducer and activator of transcription (STAT) 5 in tumor-bearing mice and hPRL-G129R also exerted an antiproliferative effect in vivo. These results indicate that hPRL-G129R is indeed a dual-function antagonist. This study lays a foundation for exploring and developing highly effective agents against the proliferation and progression of breast malignancies.

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