Prolactin receptor in breast cancer: marker for metastatic risk

Abstract

Prolactin and prolactin receptor signaling and function are complex in nature and intricate in function. Basic, pre-clinical and translational research has opened up our eyes to the understanding that prolactin and prolactin receptor signaling function differently within different cellular contexts and microenvironmental conditions. Its multiple roles in normal physiology are subverted in cancer initiation and progression, and gradually we are teasing out the intricacies of function and therapeutic value. Recently, we observed that prolactin has a role in accelerating the time to bone metastasis in breast cancer patients and identified the mechanism by which prolactin stimulated breast cancer cellmediated lytic osteoclast formation. The possibility that the prolactin receptor is a marker for metastasis, and specifically bone metastasis, is one that may have to be put into the context of the different variants of prolactin, different prolactin receptor isoforms and intricate signaling pathways that are regulated by the microenvironment. The more complete the picture, the better one can test biomarker identity and design clinical trials to test therapeutic intervention. This review will cover the recent advances and highlight the complexity of prolactin receptor biology.

Aripiprazole combination for reversal of paliperidone-induced increase in prolactin level

“…Nonetheless, an increase of prolactin levels was observed while no significant variation in the thickness of the endometrium was established. After a year of observation, we conclude that although elevated prolactin levels might affect and introduce changes in the menstrual cycle, they are unlikely to influence the thickness of the endometrium,21,22 which might be associated with the absence of Pit-1 (pituitary-specific transcription factor) expression in the endometrium 23,24. Nevertheless, the long-term influence of prolactin on the thickness of the endometrium remains to be observed.…”

Spontaneous aggressive ERα+ mammary tumor model is driven by Kras activation

“…PRL is able to initiate a diverse spectrum of signals apart from JAK2/STAT5, including activation of Src and downstream pathways, and crosstalk with the Ras cascade itself (Barcus et al, 2013;Erwin et al, 1995;Martín-Pérez et al, 2015) . These observations likely account for the controversy surrounding the role of PRL signals in clinical disease (Hachim et al, 2016;Shemanko, 2016) .…”

JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

“…Similar to other cytokine receptors, PRLR signaling involves several receptor-associated kinases [17-19]. The Janus tyrosine kinase 2 (JAK2) is constitutively associated with PRLR and plays a central role in PRLR signaling.…”