Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.
Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.
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DOI：
10.1016/j.jsbmb.2017.04.011
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Lange CA
中科院分区：
文献类型：
--
作者：
Leehy KA;Truong TH;Mauro LJ;Lange CA
雌激素是青春期乳腺发育的主要促有丝分裂刺激物，其中ER信号传导作用于诱导丰富的PR表达。相反，PR信号是成年期乳腺上皮细胞增殖的主要驱动力。妊娠期间孕酮的高循环水平通过PR发出信号，诱导催乳素受体（PRLR）的表达。PR和催乳素（PRL）信号之间的合作，通过调节PRL信号通路中的下游组分，包括JAK和STAT，促进妊娠期间观察到的肺泡形态发生。事实上，这些途径通过激活共享的信号传导途径（即JAK、MAPK）以及通过PR和STAT在与乳腺生物学和乳腺癌进展（即增殖、干细胞生长、组织细胞类型异质性）相关的靶基因处的会聚而完全整合。因此，而不是一个单一的介质，如ER，转录因子级联（ER>PR> STAT）是负责快速增殖和发育的正常乳腺编程。毫不奇怪，这些相同的介质代表了大多数乳腺癌中不受控制的增殖，其中ER和PR最常共表达，并可能合作推动恶性肿瘤进展。本综述将主要关注PR和PRL信号在乳腺癌模型中的整合，以及在乳腺摄影密度的背景下这种串扰在癌症进展中的重要性。这些PR/PRL信号通路的组分可以为抗ER或基于抗雌激素的内分泌疗法提供替代药物靶点和逻辑补充。
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies.
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影响因子：
10.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1093/jnci/djr079
发表时间：
2011-05-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
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通讯作者：
Warren, Ruth M. L.