Prolactin (PRL) translocation to the nucleus is a known phenomenon in patients with breast cancer. There is no evidence of this phenomenon in domestic animals (like pigs) at this time. Furthermore, a comprehensive understanding of the molecular mechanisms driving PRLR nuclear translocation remains elusive. In this study, a cell model consisting of porcine mammary epithelial cells (PMECs) was developed. The induction of nuclear localization of porcine PRLR in PMECs was observed in response to porcine prolactin (pPRL). Afterwards, an analysis was conducted on the dynamics of pPRL-induced nuclear localization of pPRLR, which revealed that this process is time-dependent. After that, we utilized several pPRLR ligands to investigate how pPRLR localizes to the nucleus, and we showed that the nuclear translocation of pPRLR is PRL(s)-dependent. Additionally, we discovered that the nuclear translocation of the pPRL-PRLR complex is influenced by importin β1 (IMP β1), and EEA1 was involved in the nuclear translocation of pPRL-PRLR complex. In cell nuclei, the pPRL-PRLR complex has the potential to form a pPRL-PRLR-JAK2 multimer complex, suggesting that the nuclear-localized pPRL-PRLR complex may remain capable of transmitting signals, analogous to its function in the cell membrane.
Read full abstract