Expression of a constitutively active prolactin receptor causes histone trimethylation of

Expression of a constitutively active prolactin receptor causes histone trimethylation of the p53

gene in breast cancer

Tan Dunyong;Tang Peizhi;Huang Jianjun;Zhang Jie;Zhou Weihua;Ameae M.Walker

【期刊名称】《中华医学杂志（英文版）》 【年(卷),期】2014(127)006

【摘要】Background Prolactin (PRL) is a pituitary polypeptide hormone characterized by multiple biological actions including stimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression in the mammary gland.PRL exerts its effect by dimerizing its receptor (PRLR) on the plasma membrane and regulating gene expression through the JAK-Stat signal pathway.We have previously described a natural variant of the PRLR in which the S2 subdomain of the extracellular domain is missing (Delta S2).Delta S2 PRLRs are dimerized in the absence of PRL and have constitutive activity in the promotion of breast cancer cell growth.Enhancer of zeste homolog 2 (EZH2),as one of the histone-modifying enzymes,is a key factor regulating gene expression by epigenetic modification.We hypothesized that these constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in the expression of EZH2 and the trimethylation of histone 3 on lysine 27 (H3K27Me3).Methods In order