Differential expression of cytoplasmic and stromal β-arrestin-1 is associated with separate aspects of tumor behavior in breast cancer
© BioMed Central Ltd. 2009
Published: 23 June 2009
The main focus of our study was to investigate the importance of β-arrestin-1 in breast cancer and to elucidate a possible link between β-arrestin-1 protein overexpression and CCND1 amplification, since both genes map to chromosome locus 11q13, a region often amplified in breast cancer.
The β-arrestin-1 protein expression was assessed in two different patient cohorts. The first included 179 premenopausal and postmenopausal breast cancer patients and the second included 500 breast cancer cases from premenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment.
High cytoplasmic expression of β-arrestin-1 turned out to be associated with estrogen receptor negativity and HER2 amplification, whereas high β-arrestin-1 expression in stromal cells was associated with a more aggressive tumor phenotype. In the randomized cohort, cytoplasmic β-arrestin-1 expression was inversely correlated to amplification of CCND1 and positively correlated to expression of Chk1, previously described as a marker for distal 11q deletion, implying that the ARRB1 gene, instead of being co-amplified, might be deleted in the 11q13 amplification event.
Interestingly, β-arrestin-1 may play different roles for tumor cells, depending on whether it is expressed by the tumor cell itself or by the surrounding stroma. In addition, amplification of the CCND1 gene might be associated with a loss of the ARRB1 gene.