The role of prolactin and its antagonist in HER2/neu tumorigenesis

摘要: Purpose: To study the role of prolactin (PRL) and its antagonist, G129R, in HER2/Neu tumorigenesis. Specifically, to investigate interaction between oncogene HER2 PRL receptor (PRLR) signaling pathways for designing effective combinational therapeutics breast cancer. Experimental Design: The combination effects G129R an anti-HER2 antibody, Herceptin, were tested against HER2-overexpressing human cancer cell lines, T-47D BT-474, using based assays xenografts established athymic mice. Furthermore, four different bitransgenic mouse lines co-expressing murine version or generated. mammary tumor incidence, characterization gland development, alteration molecular biomarkers glands investigated these transgenic Results: It was demonstrated that able activate cells addition competitively inhibited stimulatory effect hPRL. More importantly, has synergistic/additive when used with Herceptin inhibiting activation. Results further demonstrate displayed a synergistic inhibitory on MAPK phosphorylation. Most treatment significantly growth In study, it found co-expression MMTV-neu female mice had little overall incidence due low expression levels G129R. Surprisingly,