Our studies have demonstrated the essential role of endogenous PRL and CDK7 in the upregulation of PRLR by E2 and provide insights for therapeutic approaches that will mitigate the transcription/expression of PRLR and its participation in breast cancer progression fueled by E2 and PRL via their cognate receptors.
Prolactin induction of Class II HLA Ag expression by human breast cancer cell lines should prove very useful to study the biology of prolactin in the tumorogenesis of the human breast.
Here, we examined a mouse model of prolactin-induced aggressive ERα<sup>+</sup> breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα<sup>+</sup> tumors.
We added a breast cancer PRS using 67 single nucleotide polymorphisms, MD, and circulating testosterone, estrone sulfate, and prolactin levels to existing risk models.
Despite the growing body of evidence supporting prolactin (PRL) actions in human breast cancer, little is known regarding PRL regulation of its own receptor in these cells.
These studies indicate a role for paracrine EGF via EGFR independent of estrogen and prolactin in the transcriptional activation of PRLR gene expression and its contribution to high levels of PRLRs in breast cancer.
Despite the important roles of both prolactin (PRL) and 17beta-estradiol (E2) in normal mammary development as well as in breast cancer, and coexpression of the estrogen receptor (ER) and PRL receptor in many mammary tumors, the interactions between PRL and E2 in breast cancer have not been well studied.
The mammotrophic hormone, prolactin (PRL), and/or its receptor are also expressed in many breast cancers, and accumulating epidemiologic data link PRL to breast cancer development and progression.
These data suggest that Nek3 contributes to PRL-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.
Aromatase, never in mitosis A-related kinase 3 (NEK3), protein inhibitor of activated STAT3 (PIAS3), and prolactin are known as upregulated proteins in breast cancer.
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 cell-mediated lytic osteoclast formation.
Owing to the upregulation of the PRLR and the local synthesis of its ligand in neoplastic cells, it has been proposed that PRL can act as a local growth factor in human breast cancers.
A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling.
The analytical quantification and follow-up of the hormone prolactin is very important in clinical diagnosis (e.g., in cases of breast cancer), treatment, and the medical laboratory.
These studies highlight the utility of these models to decipher the interplay between prolactin and other oncogenic factors in breast cancer, with implications for preventative and therapeutic strategies.
Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins.
These genomic analyses suggest that PRL induces a selective bottleneck for spontaneous Ras-driven tumors that may model a subset of aggressive clinical ER+ breast cancers.