Blockade of the Short Form of Prolactin Receptor Induces FOXO3a/EIF-4EBP1-Mediated Cell Death in Uterine Cancer.

摘要: Abnormal activity of human prolactin (PRL) and its membrane-associated receptor (PRLR) contribute to the progression uterine carcinoma. However, underlying mechanisms are not well understood, current means targeting PRL/PRLR axis in cancer limited. Our integrated analyses using TCGA GTEx databases demonstrated that a short form PRLR (PRLR_SF) is isoform predominantly expressed cancers; expression this PRLR_SF was elevated cancers comparison cancer-free tissues. We hypothesized overexpression cells contributes, part, oncogenic axis. Next, we employed G129R, an antagonist PRL, block both PTENwt PTENmut orthotopic mouse models cancer. In with control groups, treatment G129R as monotherapy or combination paclitaxel resulted significant reduction growth tumors. Results from protein profiling vivo tumors revealed set new downstream targets for G129R. Besides, our results showed induced G0/G1 arrest, decreased nascent synthesis, initiated FOXO3a/EIF-4EBP1-mediated cell death cells. Collectively, show unique pattern Moreover, FOXO3a EIF-4EBP1 important mediators following models.