Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.
Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.
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DOI：
10.1016/j.stemcr.2017.08.011
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发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Schuler LA
中科院分区：
文献类型：
--
作者：
O'Leary KA;Shea MP;Salituro S;Blohm CE;Schuler LA
Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61+ luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Local prolactin leads to metastatic estrogen receptor-expressing mammary cancer Prolactin augments mammary progenitors in the absence of estrogen/progesterone With steroids, prolactin expands stem cells associated with elevated Wnt signaling Prolactin increases ERα partners and PR-A but impedes steroid-driven maturation Elevated prolactin correlates with increased risk for aggressive breast cancers expressing ERα. In a transgenic mouse model with high mammary prolactin, Schuler and colleagues demonstrate expanded progenitor/stem epithelial populations and impeded steroid-induced luminal cell maturation, associated with altered transcriptional networks to perturb differentiation, which may underlie its contributions to this disease.
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