EGFR associated expression profiles vary with breast tumor subtype

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  • Hoadley, Katherine
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Curriculum in Genetics and Molecular Biology
  • Weigman, Victor J
    • Affiliation: College of Arts and Sciences, Department of Biology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Fan, Cheng
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Department of Genetics
  • Sawyer, Lynda R
    • Affiliation: School of Medicine, Division of Hematology/Oncology
  • He, Xiaping
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Department of Genetics
  • Troester, Melissa A
    • Other Affiliation: Department of Public Health – Biostatistics and Epidemiology Concentration, University of Massachusetts Amherst, Amherst, MA, USA
  • Sartor, Carolyn I
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Department of Radiation Oncology
  • Rieger-House, Thais
    • Other Affiliation: Huntsman Cancer Institute and Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Bernard, Philip S
    • Other Affiliation: Huntsman Cancer Institute and Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Carey, Lisa
    • Affiliation: School of Medicine, Division of Hematology/Oncology
  • Perou, Charles
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Abstract 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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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Katherine A Hoadley et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Genomics
Journal volume
  • 8
Journal issue
  • 1
Page start
  • 258
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2164
Bibliographic citation
  • BMC Genomics. 2007 Jul 31;8(1):258
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • September 6, 2012

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Thumbnail Title Date Uploaded Visibility Actions
file details 1471-2164-8-258.pdf 2019-05-06 Public Download
file details Full cluster diagram for the gene expression patterns of SUM102 cells treated with gefitinib or cetuximab. 2019-05-06 Public Download
file details Gefitinib and carboplatin combinations in breast cancer-derived cell lines. Cells were treated for 72 h with constant ratios of the IC50 doses for both gefitinib and carboplatin. Combination Index (CI) values below one are synergistic, equal to one 2019-05-06 Public Download
file details Genes from Cluster #1–3. Genes identified from the 500 SUM102 genes clustered on the UNC tumor dataset. 2019-05-06 Public Download
file details Clinical data associated with each tumor sample. 2019-05-06 Public Download
file details 1471-2164-8-258.xml 2019-05-06 Public Download
file details Full cluster diagram for the in vivo EGFR-activation profiles clustered on the UNC tumor data set. 2019-05-06 Public Download