
LINK . SPRINGER . COM {
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Title:
EGFR associated expression profiles vary with breast tumor subtype | BMC Genomics
Description:
Background The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors. Results In vitro, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed in vitro, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident in vivo, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors. Conclusion These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. In vivo, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.
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Keywords {π}
expression, breast, pubmed, cancer, cell, article, google, scholar, egfr, genes, cas, tumors, gene, tumor, basallike, lines, high, sum, cetuximab, pathway, data, cells, luminal, cluster, analysis, inhibitor, gefitinib, samples, figure, subtype, clusters, growth, inhibitors, egfrassociated, combination, line, treated, receptor, treatment, res, profiles, mek, perou, identified, performed, set, microarray, activation, carboplatin, table,
Topics {βοΈ}
high/p27 low/p53+/glomeruloid-microvascular-proliferation+ /cgi-bin/smd/publication/viewpublication her2/neu-positive breast cancers kaplan-meier survival analyses gov/ct/show/nct00232505] cytoscape open access article cox-mantel log-rank test er/her2-positive breast cancer egfr-ras-mek pathway plays extracellular ligand-binding domain article download pdf egfr-ras-mek pathway downstream brca1-related breast cancer rapamycin/4e-bp1 pathway triple-negative breast cancer tamoxifen-resistant breast cancer gene-expression-based predictors inhibits her2-driven signaling biologically targeted drugs tumor-derived cell lines cell-type-specific responses invasive breast carcinoma full size image estrogen-independent proliferation sequence-dependent antiproliferative effects bidirectional cross talk oestrogen-receptor positive her2+/er-negative β pink her2-overexpressing tumor cells human tumor samples genome-wide expression patterns egfr-dependent cell line thais rieger-house background signal intensity tyrosine kinase inhibitors egfr-pathway components relative egfr-ras-mek pathway unc microarray database chi square tests ongoing clinical trial metastatic breast cancer privacy choices/manage cookies cox multivariate analysis human cancer cells primary tumor data nki295 sample set human breast tumours chi-square analysis regulating cell growth tissue culture facility
Questions {β}
- Baselga J: Why the epidermal growth factor receptor?
- Sieuwerts AM, Look MP, Meijer-van Gelder ME, Timmermans M, Trapman AM, Garcia RR, Arnold M, Goedheer AJ, de Weerd V, Portengen H, Klijn JG, Foekens JA: Which cyclin E prevails as prognostic marker for breast cancer?
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headline:EGFR associated expression profiles vary with breast tumor subtype
description:The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors. In vitro, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed in vitro, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident in vivo, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors. These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. In vivo, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.
datePublished:2007-07-31T00:00:00Z
dateModified:2007-07-31T00:00:00Z
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Estrogen Receptor
Human Epidermal Growth Factor Receptor
Cetuximab
Gefitinib
EGFR Inhibitor
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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headline:EGFR associated expression profiles vary with breast tumor subtype
description:The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors. In vitro, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed in vitro, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident in vivo, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors. These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. In vivo, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.
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Estrogen Receptor
Human Epidermal Growth Factor Receptor
Cetuximab
Gefitinib
EGFR Inhibitor
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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name:Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Department of Public Health β Biostatistics and Epidemiology Concentration, University of Massachusetts Amherst, Amherst, USA
name:Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Huntsman Cancer Institute and Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA
name:Huntsman Cancer Institute and Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA
name:Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
name:Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA
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