摘要：SummaryThe post-menopausal state in women is associated with increased cancer incidence, the reasons for which remain obscure. Curiously, increased circulating levels of beta-hCG (human chorionic gonadotropin) (a hormonal subunit linked with tumors of several lineages) are also often observed post-menopause. This study describes a previously unidentified interplay between beta-hCG and progesterone in tumorigenesis. Progesterone mediated apoptosis in beta-hCG responsive tumor cells via non-nuclear receptors. The transgenic expression of beta-hCG, particularly in the absence of the ovaries (a mimic of the post-menopausal state) constituted a potent pro-tumorigenic signal. Significantly, the administration of progesterone had significant anti-tumor effects. RNA-seq profiling identified molecular signatures associated with these processes. TCGA analysis revealed correlates between the expression of several newly identified genes and poor prognosis in post-menopausal patients of lung adenocarcinoma, colon adenocarcinoma, and glioblastoma. Specifically in these women, the detection of intra-tumoral/extra-tumoral beta-hCG may serve as a useful prognostic indicator, and treatment with progesterone on its detection may prove beneficial.Graphical abstractDisplay OmittedHighlights•Beta-hCG (human chorionic gonadotropin) is linked with poor survival in menopausal women bearing aggressive tumors•Beta-hCG’s tumorigenic effects are amplified in the absence of the ovaries•Progesterone dampens beta-hCG-driven tumorigenesis via non-nuclear receptors•Many post-menopausal tumors preferentially express non-nuclear progesterone receptorsCancer; Cell biology; Physiology
