title: Epidermal growth factor receptor variant III contributes to cancer stem cell phenotypes in invasive breast carcinoma.
abstract: EGFRvIII is a tumor-specific variant of the epidermal growth factor receptor (EGFR). Although EGFRvIII is most commonly found in glioblastoma, its expression in other tumor types remains controversial. In this study, we investigated EGFRvIII expression and amplification in primary breast carcinoma. Our analyses confirmed the presence of EGFRvIII, but in the absence of amplification or rearrangement of the EGFR locus. Nested reverse transcriptase PCR and flow cytometry were used to detect a higher percentage of positive cases. EGFRvIII-positive cells showed increased expression of genes associated with self-renewal and epithelial-mesenchymal transition along with a higher percentage of stem-like cells. EGFRvIII also increased in vitro sphere formation and in vivo tumor formation. Mechanistically, EGFRvIII mediated its effects through the Wnt/β-catenin pathway, leading to increased β-catenin target gene expression. Inhibition of this pathway reversed the observed effects on cancer stem cell (CSC) phenotypes. Together, our findings show that EGFRvIII is expressed in primary breast tumors and contributes to CSC phenotypes in breast cancer cell lines through the Wnt pathway. These data suggest a novel function for EGFRvIII in breast tumorigenesis.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Del Vecchio
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Jensen
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Nitta
authors.forename: A Hunter
authors.initials: AH
authors.lastname: Shain
authors.forename: Craig P
authors.initials: CP
authors.lastname: Giacomini
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Wong
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D060449:Wnt Signaling Pathway
chemical_list: C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors