Argueta, Donovan A.Aich, AnupamLei, JianxunKiven, StacyNguyen, AithanhWang, YingGu, JoshuaZhao, WeianGupta, Kalpna2024-08-132024-08-132021Argueta DA, Aich A, Lei J, et al. β-endorphin at the intersection of pain and cancer progression: Preclinical evidence. Neurosci Lett. 2021;744:135601. doi:10.1016/j.neulet.2020.135601https://hdl.handle.net/1805/42754We examined the association between endogenous opioid β-endorphin, cancer progression and pain in a transgenic mouse model of breast cancer, with a rat C3(1) simian virus 40 large tumor antigen fusion gene (C3TAg). C3TAg mice develop ductal epithelial atypia at 8 weeks, progression to intra-epithelial neoplasia at 12 weeks, and invasive carcinoma with palpable tumors at 16 weeks. Consistent with invasive carcinoma at 4 months of age, C3TAg mice demonstrate a significant increase in hyperalgesia compared to younger C3TAg or control FVBN mice without tumors. Our data show that the growing tumor contributes to circulating β-endorphin. As an endogenous ligand of mu opioid receptor, β-endorphin has analgesic activity. Paradoxically, we observed an increase in pain in transgenic breast cancer mice with significantly high circulating and tumor-associated β-endorphin. Increased circulating β-endorphin correlates with increasing tumor burden. β-endorphin induced the activation of mitogenic and survival-promoting signaling pathways, MAPK/ERK 1/2, STAT3 and Akt, observed by us in human MDA-MB-231 cells suggesting a role for β-endorphin in breast cancer progression and associated pain.en-USPublisher Policyβ-endorphinBreast cancerPainMorphineOpioidArticle