Mechanisms of EGF receptor regulation in breast cancer cells.
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.
Chrysogelos
S A
SA
Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007.
Yarden
R I
RI
Lauber
A H
AH
Murphy
J M
JM
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000235:genetics / Q000473:pathology
D004967:Estrogens; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D004815:Epidermal Growth Factor; D066246:ErbB Receptors