title: Identification and functional validation of RAD23B as a potential protein in human breast cancer progression.
abstract: 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.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University , Glasnevin, Dublin 9, Ireland.
authors.forename: Annett
authors.initials: A
authors.lastname: Linge
authors.forename: Priyanka
authors.initials: P
authors.lastname: Maurya
authors.forename: Katrin
authors.initials: K
authors.lastname: Friedrich
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Baretton
authors.forename: Shane
authors.initials: S
authors.lastname: Kelly
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
authors.forename: Annemarie
authors.initials: A
authors.lastname: Larkin
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D011960:Receptors, Estrogen / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; D011960:Receptors, Estrogen; D045643:DNA Repair Enzymes