Abstract
Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER-/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNAse I hypersensitive site patterns for the EGFR gene in ER+ vs. ER- cells implicates regions of the EGFR first intron in up-regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER-/EGFR+ stage.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / mortality
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Carcinoma / genetics
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Carcinoma / pathology
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Disease Progression
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Down-Regulation / drug effects
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Epidermal Growth Factor / physiology
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ErbB Receptors / biosynthesis*
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ErbB Receptors / drug effects
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ErbB Receptors / genetics
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ErbB Receptors / physiology
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Estrogens / pharmacology
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplasms, Hormone-Dependent / genetics
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Neoplasms, Hormone-Dependent / metabolism
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Prognosis
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Receptors, Estrogen / analysis
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Tumor Cells, Cultured
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Vulvar Neoplasms / genetics
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Vulvar Neoplasms / pathology
Substances
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Estrogens
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Neoplasm Proteins
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Receptors, Estrogen
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Epidermal Growth Factor
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ErbB Receptors