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ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis

Svensson Månsson, Sofie LU ; Jirström, Karin LU ; Rydén, Lisa LU ; Roos, G; Emdin, S; Ostrowski, M and Landberg, Göran LU (2005) In Oncogene 24(27). p.4370-4379
Abstract
Extracellular signal-regulated kinase (ERK) 1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinicopathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients,... (More)
Extracellular signal-regulated kinase (ERK) 1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinicopathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients, cohort II of 248 postmenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment and cohort III of 524 patients. Surprisingly, ERK1/2 phosphorylation correlated inversely with tumour size. Phosphorylated ERK1/2 was further associated with the presence of VEGFR2 (cohorts II and III) and the degree of phosphorylated Ets-2, indicating in vivo, a signalling cascade from VEGFR2 via ERK1/2 to Ets-2 phosphorylation. Interestingly, ERK1/2 phosphorylation correlated with better survival in untreated patients independently of lymph- node status and tumour size indicating that ERK1/2 signalling might be associated with a less aggressive phenotype. Finally, patients with oestrogen receptor positive and ERK1/2 phosphorylated tumours also had an impaired tamoxifen response. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
tamoxifen, prognosis, ERK, breast cancer, MAPK, Ets-2, VEGF, proliferation, VEGFR2
in
Oncogene
volume
24
issue
27
pages
4370 - 4379
publisher
Nature Publishing Group
external identifiers
  • pmid:15806151
  • wos:000229976900006
  • scopus:21744453318
ISSN
1476-5594
DOI
10.1038/sj.onc.1208626
language
English
LU publication?
yes
id
02b5dbf1-d5c1-4d44-91ac-1b731ce49f96 (old id 235532)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15806151&dopt=Abstract
date added to LUP
2007-08-13 09:48:13
date last changed
2017-07-02 03:36:48
@article{02b5dbf1-d5c1-4d44-91ac-1b731ce49f96,
  abstract     = {Extracellular signal-regulated kinase (ERK) 1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinicopathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients, cohort II of 248 postmenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment and cohort III of 524 patients. Surprisingly, ERK1/2 phosphorylation correlated inversely with tumour size. Phosphorylated ERK1/2 was further associated with the presence of VEGFR2 (cohorts II and III) and the degree of phosphorylated Ets-2, indicating in vivo, a signalling cascade from VEGFR2 via ERK1/2 to Ets-2 phosphorylation. Interestingly, ERK1/2 phosphorylation correlated with better survival in untreated patients independently of lymph- node status and tumour size indicating that ERK1/2 signalling might be associated with a less aggressive phenotype. Finally, patients with oestrogen receptor positive and ERK1/2 phosphorylated tumours also had an impaired tamoxifen response.},
  author       = {Svensson Månsson, Sofie and Jirström, Karin and Rydén, Lisa and Roos, G and Emdin, S and Ostrowski, M and Landberg, Göran},
  issn         = {1476-5594},
  keyword      = {tamoxifen,prognosis,ERK,breast cancer,MAPK,Ets-2,VEGF,proliferation,VEGFR2},
  language     = {eng},
  number       = {27},
  pages        = {4370--4379},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis},
  url          = {http://dx.doi.org/10.1038/sj.onc.1208626},
  volume       = {24},
  year         = {2005},
}