Epidermal Growth Factor Receptor Variant III Contributes to Cancer Stem Cell Phenotypes in Invasive Breast Carcinoma

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....

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2012-05, Vol.72 (10), p.2657-2671
Main Authors: DEL VECCHIO, Catherine A, JENSEN, Kristin C, NITTA, Ryan T, HUNTER SHAIN, A, GIACOMINI, Craig P, WONG, Albert J
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor
Epithelial-Mesenchymal Transition - genetics
Female
Genes, erbB-1
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Mice
Neoplasm Transplantation
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Pharmacology. Drug treatments
Phenotype
Receptor, Epidermal Growth Factor - genetics
Tumors
Wnt Signaling Pathway
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-11-2656