Identification and characterization of a negative regulatory element within the epidermal growth factor receptor gene first intron in hormone-dependent breast cancer cells
| Autor: | Melissa A. Wilson, Susan A. Chrysogelos |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Neoplasms
Hormone-Dependent Transcription Genetic Negative regulatory element Estrogen receptor Breast Neoplasms Biology Regulatory Sequences Nucleic Acid Biochemistry Breast cancer Downregulation and upregulation Estrogen Receptor Modulators Gene expression medicine Transcriptional regulation Tumor Cells Cultured Humans ERBB3 Epidermal growth factor receptor Molecular Biology Fulvestrant Estradiol Estrogens Cell Biology medicine.disease Molecular biology Introns ErbB Receptors Gene Expression Regulation Neoplastic Receptors Estrogen Cancer research biology.protein Female |
| Zdroj: | Journal of cellular biochemistry. 85(3) |
| ISSN: | 0730-2312 |
| Popis: | 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. J. Cell. Biochem. 85: 601–614, 2002. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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