Identification and characterization of a negative regulatory element within the epidermal growth factor receptor gene first intron in hormone-dependent breast cancer cells.

Abstract:

:The epidermal growth factor receptor (EGFR) exhibits an inverse correlation with estrogen receptor (ER) expression in the majority of breast cancers, predicting a poor response to endocrine therapy and poor survival rate. Inappropriate overexpression of EGFR in breast cancer is associated with a more aggressive phenotype. Transcriptional regulation is the major regulatory mechanism controlling EGFR overexpression in breast cancer cells. We have identified a region within the first intron of the EGFR gene that mediates transcriptional repression of EGFR gene expression in ER +/low EGFR expressing but not in ER-/high EGFR expressing breast cancer cells. Utilizing transient transfections of homologous and heterologous promoter-reporter constructs, we localized optimal repressive activity to a 96 bp intron domain. The 96 bp fragment displayed differential DNA-protein complex formation with nuclear extracts from ER + vs. ER- breast cancer cells. Moreover, factors interacting with this intron negative regulatory element appear to be estrogen-regulated. Consequently, our results suggest that we have identified a potential mechanism by which maintenance of low levels of EGFR expression and subsequent EGFR upregulation may be attributed to the loss of transcriptional repression of EGFR gene expression in hormone-dependent breast cancer cells.

journal_name

J Cell Biochem

authors

Wilson MA,Chrysogelos SA

doi

10.1002/jcb.10168

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

601-14

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

85

pub_type

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