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EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation.

Reinbothe, Susann LU ; Larsson, Anna-Maria LU ; Vaapil, Marica LU ; Wigerup, Caroline LU ; Sun, Jianmin LU ; Jögi, Annika LU ; Neumann, Drorit; Rönnstrand, Lars LU and Påhlman, Sven LU (2014) In Biochemical and Biophysical Research Communications 445(1). p.163-169
Abstract
The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent... (More)
The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα(+)) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
445
issue
1
pages
163 - 169
publisher
Elsevier
external identifiers
  • pmid:24502950
  • wos:000332749400028
  • scopus:84896699458
ISSN
1090-2104
DOI
10.1016/j.bbrc.2014.01.165
language
English
LU publication?
yes
id
375bb03f-adb7-42ca-8635-52429ad46db1 (old id 4335460)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24502950?dopt=Abstract
date added to LUP
2014-03-06 19:49:50
date last changed
2017-10-22 03:18:05
@article{375bb03f-adb7-42ca-8635-52429ad46db1,
  abstract     = {The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα(+)) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.},
  author       = {Reinbothe, Susann and Larsson, Anna-Maria and Vaapil, Marica and Wigerup, Caroline and Sun, Jianmin and Jögi, Annika and Neumann, Drorit and Rönnstrand, Lars and Påhlman, Sven},
  issn         = {1090-2104},
  language     = {eng},
  number       = {1},
  pages        = {163--169},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2014.01.165},
  volume       = {445},
  year         = {2014},
}