title: The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells.
abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel. Electronic address: Oritu@clalit.org.il.
authors.forename: Orit
authors.initials: O
authors.lastname: Uziel
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel; Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Kanfer
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Beery
authors.affiliation: Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Yelin
authors.affiliation: Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Shepshelovich
authors.affiliation: Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Mary
authors.initials: M
authors.lastname: Bakhanashvili
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel; Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel; Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva, Israel.
authors.forename: Jardena
authors.initials: J
authors.lastname: Nordenberg
authors.affiliation: Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel; Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Lahav
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D041905:Erythroid Cells / Q000378:metabolism / Q000473:pathology; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D059506:Telomere Shortening / Q000187:drug effects*
chemical_list: D004921:Erythropoietin; D019098:Telomerase
keywords: Erythropoietin; Lyn-src; Telomerase; Telomeres