4.7 Article

Oxytocin receptor induces mammary tumorigenesis through prolactin/p-STAT5 pathway

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CELL DEATH & DISEASE
卷 12, 期 6, 页码 -

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SPRINGERNATURE
DOI: 10.1038/s41419-021-03849-8

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  1. National Natural Science Foundation of China [81270953, 31301189]
  2. Natural Science Foundation of Jilin Province [20200201127JC]

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The study using a transgenic mouse model of OXTR overexpression found that OXTR can promote mammary hyperplasia and tumorigenesis, as well as creating a microenvironment that promotes tumor growth, providing potential for targeted therapy in HER2-type breast cancer.
Oxytocin receptor (OXTR) is involved in social behaviors, thermoregulation, and milk ejection, yet little is known about its role in breast cancer. To investigate the role of OXTR in mammary gland development and tumorigenesis, a transgenic mouse model of OXTR overexpression ((++)Oxtr) was used. Overexpression of OXTR-induced progressive mammary hyperplasia, unexpected milk production, and tumorigenesis in females. OXTR-induced mammary tumors showed ERBB2 upregulation and mixed histological subtypes with predomination of papillary and medullary carcinomas. OXTR overexpression led to an activation of prolactin (PRL)/p-STAT5 pathway and created a microenvironment that promotes mammary-specific tumorigenesis. PRL inhibitor bromocriptine (Br) could mitigate OXTR-driven mammary tumor growth. The study demonstrates Oxtr is an oncogene and a potential drug target for HER2-type breast cancer.

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