Identification and Functional Validation of RAD23B as a Potential Protein in Human Breast Cancer Progression

Identification
of protein targets that play a role in breast cancer
invasion may help to understand the rapid progression of cancer and
may lead to the development of new biomarkers for the disease. In
this study, we compared two highly invasive and two poorly invasive
breast cancer cell lines using comparative label-free LC–MS
profiling in order to identify differentially expressed proteins that
may be linked to the invasive phenotype in vitro. Forty-five proteins
were found to be upregulated, and 34 proteins, downregulated. UV excision
repair protein RAD23 homologue B (RAD23B) was found among the downregulated
proteins in highly invasive breast cancer cell lines. In poorly invasive
breast cancer cell lines, siRNA-mediated downregulation of RAD23B
subsequently led to an increase in invasion and adhesion in vitro.
Immunohistochemistry analysis of 164 specimens of invasive breast
cancer showed that having a high percentage (>80%) of RAD23B positive
nuclei was significantly associated with histopathological grades
1 and 2 breast cancer and with low mitotic activity. In addition,
a high staining intensity for RAD23B in the cytoplasm was significantly
associated with histopathological grade 3 breast cancer. This study
suggests a potential role of RAD23B in breast cancer progression and
may further imply a tumor suppressor role of nuclear RAD23B in breast
cancer.