Stromal expression of β-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer.

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.

• Authors: Katja Lundgren, Nicholas P Tobin, Sophie Lehn, Olle Stål, Lisa Rydén, Karin Jirström, Göran Landberg
• Journal: The Journal of molecular diagnostics : JMD (J Mol Diagn) Vol. 13 Issue 3 Pg. 340-51 (May 2011) ISSN: 1943-7811 [Electronic] United States
• PMID: 21497294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• ARRB1 protein, human
• Arrestins
• Biomarkers, Tumor
• beta-Arrestin 1
• beta-Arrestins
• Tamoxifen
• Cyclin D1
• Protein Kinases
• Checkpoint Kinase 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Arrestins (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (diagnosis, drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Checkpoint Kinase 1
• Cyclin D1 (genetics, metabolism)
• Female
• Gene Amplification (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Middle Aged
• Prognosis
• Protein Kinases (genetics, metabolism)
• Stromal Cells (drug effects, metabolism, pathology)
• Survival Analysis
• Tamoxifen (pharmacology, therapeutic use)
• Treatment Outcome
• beta-Arrestin 1
• beta-Arrestins