Proteomic analysis of breast cancer tissue reveals upregulation of actin-remodeling proteins and its relevance to cancer invasiveness

Abstract

There is an emerging interest in protein expression profiling with the aim of identifying novel diagnostic markers and therapeutic targets in breast cancer. We analyzed breast cancer tissues by 2-D DIGE using a narrow range IPG strip (pH 5.5-6.7) after the immunodepletion of serum albumin and Ig. Sixty-three protein spots were detected with more than +/- 1.8-fold differences (p < 0.05 for three technical replicates) from a set of tissue samples in which three tumor and three nontumor samples were randomly selected from six breast cancer subjects and pooled separately. Of these, 53 proteins were successfully identified by MS. Among the proteins whose levels were increased, we identified three novel WD-repeat-motifbearing proteins that have been known to be involved in actin remodeling: Arp2/3 complex subunit 2 (p34-Arc), coronin-1A and WD-repeat protein 1 (Wdr1). Significantly increased amounts of p34-Arc and coronin-1A in breast cancer were also shown by Western blot analysis of matched tumor and nontumor tissue samples (N = 11, p <0.05), and were consistent with the mRNA levels retrieved from publicly available microarray databases. The siRNA knockdown of p34-Arc attenuated the invasion of SK-BR3 breast cancer cells into Matrigel. In contrast, the overexpression of coronin-1A increased this invasive activity. Taken together, the cellular levels of p34-Arc and coronin-1A were linked to cancer development and migration. The data obtained from the present study provides new insight into the management of breast cancer.