We added a breast cancer PRS using 67 single nucleotide polymorphisms, MD, and circulating testosterone, estrone sulfate, and prolactin levels to existing risk models.
The importance of prolactin (PRL) in physiological proliferation and differentiation of the mammary gland, together with high levels of PRL receptors in breast tumors, the association of circulating PRL with incidence of breast cancer, and the recognition of locally produced PRL, point to the need for greater understanding of PRL actions in mammary disease.
Breast cancer ORs (95% CI) were 0.85 (0.51-1.43) for estradiol, 0.86 (0.67-1.09) for testosterone, 0.89 (0.71-1.13) for androstenedione, 0.97 (0.71-1.34) for hCG, 0.93 (0.75, 1.15) for prolactin, 1.00 (0.78-1.27) for PlGF and 1.91 (1.00-3.65 ALSPAC) and 0.94 (0.73-1.21 MoBa) for sFlt-1, and were similar adjusting for potential confounders.
A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (Rh2 > or = 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC.
We have previously demonstrated that a hPRL antagonist (hPRL-G129R) was able to inhibit PRL induced breast cancer cell proliferation through induction of apoptosis.
In conclusion, PRL receptor mutations do not appear to be common in human breast cancer, suggesting that constitutive activation of the PRL receptor can be excluded as a major cause of mammary tumor genesis.
The demonstration of PRL-induced proteins (PIP) might be a better sign of PRL sensitivity than the existence or PRL-R; PIP have been found by Northern blot analysis in 47% of 70 breast cancers.
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.
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.
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.
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.
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.