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Stromal Expression of β-Arrestin-1 Predicts Clinical Outcome and Tamoxifen Response in Breast Cancer.

Lundgren, Katja LU ; Tobin, Nicholas P LU ; Lehn, Sophie LU ; Stål, Olle; Rydén, Lisa LU ; Jirström, Karin LU and Landberg, Göran LU (2011) In The Journal Of Molecular Diagnostics 13(3). p.340-351
Abstract
The G-protein coupled receptor associated protein β-arrestin-1 is crucial for the regulation of numerous biological processes involved in cancer progression, such as intracellular signaling and cell motility. The encoding gene ARRB1 is harbored in the same chromosomal region as the CCND1 gene (11q13). Amplification of CCND1, frequently encountered in breast cancer, often involves coamplification of additional oncogenes, as well as deletion of distal 11q genes. We investigated the clinical relevance of β-arrestin-1 in breast cancer and elucidated a potential link between β-arrestin-1 expression and CCND1 amplification. β-Arrestin-1 protein expression was evaluated in two breast cancer patient cohorts, comprising 179 patients (cohort I) and... (More)
The G-protein coupled receptor associated protein β-arrestin-1 is crucial for the regulation of numerous biological processes involved in cancer progression, such as intracellular signaling and cell motility. The encoding gene ARRB1 is harbored in the same chromosomal region as the CCND1 gene (11q13). Amplification of CCND1, frequently encountered in breast cancer, often involves coamplification of additional oncogenes, as well as deletion of distal 11q genes. We investigated the clinical relevance of β-arrestin-1 in breast cancer and elucidated a potential link between β-arrestin-1 expression and CCND1 amplification. β-Arrestin-1 protein expression was evaluated in two breast cancer patient cohorts, comprising 179 patients (cohort I) and 500 patients randomized to either tamoxifen or no adjuvant treatment (cohort II). Additionally, migration after β-arrestin-1 overexpression or silencing was monitored in two breast cancer cell lines. Overexpression of β-arrestin-1 reduced the migratory propensity of both cell lines, whereas silencing increased migration. In cohort I, high expression of stromal β-arrestin-1 was linked to reduced patient survival, whereas in cohort II both high and absent stromal expression predicted a poor clinical outcome. Patients exhibiting low or moderate levels of stromal β-arrestin-1 did not benefit from tamoxifen, in contrast to patients exhibiting absent or high expression. Furthermore, CCND1 amplification was inversely correlated with tumor cell expression of β-arrestin-1, indicating ARRB1 gene deletion in CCND1-amplified breast cancers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal Of Molecular Diagnostics
volume
13
issue
3
pages
340 - 351
publisher
Elsevier Inc.
external identifiers
  • wos:000298306400012
  • pmid:21497294
  • scopus:79955009165
ISSN
1525-1578
DOI
10.1016/j.jmoldx.2011.01.009
language
English
LU publication?
yes
id
f022be0c-70c3-43f7-a6cc-042bf4885da2 (old id 1937057)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21497294?dopt=Abstract
date added to LUP
2011-05-02 14:45:27
date last changed
2017-06-18 04:10:19
@article{f022be0c-70c3-43f7-a6cc-042bf4885da2,
  abstract     = {The G-protein coupled receptor associated protein β-arrestin-1 is crucial for the regulation of numerous biological processes involved in cancer progression, such as intracellular signaling and cell motility. The encoding gene ARRB1 is harbored in the same chromosomal region as the CCND1 gene (11q13). Amplification of CCND1, frequently encountered in breast cancer, often involves coamplification of additional oncogenes, as well as deletion of distal 11q genes. We investigated the clinical relevance of β-arrestin-1 in breast cancer and elucidated a potential link between β-arrestin-1 expression and CCND1 amplification. β-Arrestin-1 protein expression was evaluated in two breast cancer patient cohorts, comprising 179 patients (cohort I) and 500 patients randomized to either tamoxifen or no adjuvant treatment (cohort II). Additionally, migration after β-arrestin-1 overexpression or silencing was monitored in two breast cancer cell lines. Overexpression of β-arrestin-1 reduced the migratory propensity of both cell lines, whereas silencing increased migration. In cohort I, high expression of stromal β-arrestin-1 was linked to reduced patient survival, whereas in cohort II both high and absent stromal expression predicted a poor clinical outcome. Patients exhibiting low or moderate levels of stromal β-arrestin-1 did not benefit from tamoxifen, in contrast to patients exhibiting absent or high expression. Furthermore, CCND1 amplification was inversely correlated with tumor cell expression of β-arrestin-1, indicating ARRB1 gene deletion in CCND1-amplified breast cancers.},
  author       = {Lundgren, Katja and Tobin, Nicholas P and Lehn, Sophie and Stål, Olle and Rydén, Lisa and Jirström, Karin and Landberg, Göran},
  issn         = {1525-1578},
  language     = {eng},
  number       = {3},
  pages        = {340--351},
  publisher    = {Elsevier Inc.},
  series       = {The Journal Of Molecular Diagnostics},
  title        = {Stromal Expression of β-Arrestin-1 Predicts Clinical Outcome and Tamoxifen Response in Breast Cancer.},
  url          = {http://dx.doi.org/10.1016/j.jmoldx.2011.01.009},
  volume       = {13},
  year         = {2011},
}