Proteomic characterization of Her2/neu-overexpressing breast cancer cells

Hexin Chen, Genaro Pimienta, Yiben Gu, Xu Sun, Jianjun Hu, Min Sik Kim, Raghothama Chaerkady, Marjan Gucek, Robert N. Cole, Saraswati Sukumar, Akhilesh Pandey

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The receptor tyrosine kinase HER2 is an oncogene amplified in invasive breast cancer and its overexpression in mammary epithelial cell lines is a strong determinant of a tumorigenic phenotype. Accordingly, HER2-overexpressing mammary tumors are commonly indicative of a poor prognosis in patients. Several quantitative proteomic studies have employed two-dimensional gel electrophoresis in combination with MS/MS, which provides only limited information about the molecular mechanisms underlying HER2/neu signaling. In the present study, we used a SILAC-based approach to compare the proteomic profile of normal breast epithelial cells with that of Her2/neu-overexpressing mammary epithelial cells, isolated from primary mammary tumors arising in mouse mammary tumor virus-Her2/neu transgenic mice. We identified 23 proteins with relevant annotated functions in breast cancer, showing a substantial differential expression. This included overexpression of creatine kinase, retinol-binding protein 1, thymosin 4 and tumor protein D52, which correlated with the tumorigenic phenotype of Her2-overexpressing cells. The differential expression pattern of two genes, gelsolin and retinol binding protein 1, was further validated in normal and tumor tissues. Finally, an in silico analysis of published cancer microarray data sets revealed a 23-gene signature, which can be used to predict the probability of metastasis-free survival in breast cancer patients.

Original languageEnglish (US)
Pages (from-to)3800-3810
Number of pages11
JournalProteomics
Volume10
Issue number21
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

Proteomics
Tumors
Cells
Breast Neoplasms
Cellular Retinol-Binding Proteins
Breast
Epithelial Cells
Genes
Gelsolin
Thymosin
Mouse mammary tumor virus
Phenotype
Neoplasms
Electrophoresis, Gel, Two-Dimensional
Receptor Protein-Tyrosine Kinases
Microarrays
Creatine Kinase
Electrophoresis
Viruses
Oncogenes

Keywords

  • Biomedicine
  • Cancer biomarker
  • Her2
  • Quantitative proteomics SILAC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Proteomic characterization of Her2/neu-overexpressing breast cancer cells. / Chen, Hexin; Pimienta, Genaro; Gu, Yiben; Sun, Xu; Hu, Jianjun; Kim, Min Sik; Chaerkady, Raghothama; Gucek, Marjan; Cole, Robert N.; Sukumar, Saraswati; Pandey, Akhilesh.

In: Proteomics, Vol. 10, No. 21, 01.11.2010, p. 3800-3810.

Research output: Contribution to journalArticle

Chen, H, Pimienta, G, Gu, Y, Sun, X, Hu, J, Kim, MS, Chaerkady, R, Gucek, M, Cole, RN, Sukumar, S & Pandey, A 2010, 'Proteomic characterization of Her2/neu-overexpressing breast cancer cells', Proteomics, vol. 10, no. 21, pp. 3800-3810. https://doi.org/10.1002/pmic.201000297
Chen H, Pimienta G, Gu Y, Sun X, Hu J, Kim MS et al. Proteomic characterization of Her2/neu-overexpressing breast cancer cells. Proteomics. 2010 Nov 1;10(21):3800-3810. https://doi.org/10.1002/pmic.201000297
Chen, Hexin ; Pimienta, Genaro ; Gu, Yiben ; Sun, Xu ; Hu, Jianjun ; Kim, Min Sik ; Chaerkady, Raghothama ; Gucek, Marjan ; Cole, Robert N. ; Sukumar, Saraswati ; Pandey, Akhilesh. / Proteomic characterization of Her2/neu-overexpressing breast cancer cells. In: Proteomics. 2010 ; Vol. 10, No. 21. pp. 3800-3810.
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