Faculty Collaboration Database

Differential expression of arrestins is a predictor of breast cancer progression and survival. Breast Cancer Res Treat 2011 Dec;130(3):791-807

Date

02/15/2011

Pubmed ID

21318602

Pubmed Central ID

PMC3156829

DOI

10.1007/s10549-011-1374-9

Scopus ID

2-s2.0-82255163335 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Emerging evidence has implicated G protein-coupled receptors, such as CXCR4 and PAR2, in breast cancer progression and the development of metastatic breast cancer. However, the role of proteins that regulate the function of these receptors, such as arrestins, in breast cancer has yet to be determined. Examination of the expression of the two nonvisual arrestins, arrestin2 and 3, in various breast cancer cell lines revealed comparable expression of arrestin3 in basal and luminal lines while arrestin2 expression was much higher in the luminal lines compared to the more aggressive basal lines. Analysis of normal human breast tissue revealed that arrestin2 and 3 were expressed in both luminal and myoepithelial cells of mammary epithelia with arrestin2 highest in myoepithelial cells and arrestin3 comparable in both cell types. Quantitative immunofluorescence-based examination of primary breast tumors revealed that arrestin2 expression significantly decreased with cancer progression from ductal carcinoma in situ to invasive carcinoma and further to lymph node metastasis (P < 0.001). Moreover, decreased arrestin2 expression was associated with decreased survival (P = 0.0007) as well as positive lymph node status and increased tumor size and nuclear grade. In contrast, arrestin3 expression significantly increased during breast cancer progression (P < 0.001) and increased expression was associated with decreased survival (P = 0.014). Arrestin3 was also an independent prognostic marker of breast cancer with a hazard ratio of 1.65. Overall, these studies demonstrate that arrestin2 levels decrease while arrestin3 levels increase during breast cancer progression and these changes correlate with a poor clinical outcome.

Author List

Michal AM, Peck AR, Tran TH, Liu C, Rimm DL, Rui H, Benovic JL

MESH terms used to index this publication - Major topics in bold

Arrestins
Biomarkers, Tumor
Breast Neoplasms
Cell Line, Tumor
Disease Progression
Epithelial Cells
Female
Gene Expression Regulation, Neoplastic
Humans
Mammary Glands, Human
Neoplasm Invasiveness
Prognosis
Survival Analysis