CGB activates ERK and AKT kinases in cancer cells via LHCGR-independent mechanism.

Expression of human chorionic gonadotropin free beta subunit (hCGβ) and its hyperglycosylated variant (hCGβ-H) is a phenomenon confirmed for tumors of different origin. Despite numerous studies, the mechanism of hCGβ action in cancer remains unknown especially that not all tumors secreting hCGβ express the receptor for human chorionic gonadotropin (LHCGR). In the presented study, we verified the hypothesis of hCGβ potential to activate signaling pathways involving extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) kinases with and without the contribution of LHCGR. To achieve this goal, human ovarian carcinoma cells OVCAR-3 expressing LHCGR and SKOV-3 not expressing LHCGR were either transfected with a vector coding for hCGβ or stimulated with recombinant hCGβ and the level of pERK and pAKT was measured. The results of the experiments showed that hCGβ action leads to the increase in ERK and AKT kinases phosphorylation in cancer cells and indicate that these biological effects can be achieved independently of LHCGR presence. The study also demonstrated that the presence of the receptor is a key factor influencing the magnitude of cells' response.