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Title: The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - 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 tomore » 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.« less
Authors:
 [1] ;  [1] ;  [2] ;  [1] ; ;  [3] ;  [4] ;  [1] ;  [2] ;  [2] ;  [1] ;  [2]
  1. Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)
  2. (Israel)
  3. Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)
  4. Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel)
Publication Date:
OSTI Identifier:
22416628
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOCHEMISTRY; BIOLOGY; CELL CYCLE; CELL PROLIFERATION; ENZYMES; ERYTHROPOIETIN; INHIBITION; NEOPLASMS; SENSITIVITY; TELOMERES