Protein Expression Profiling of Primary Mammary Epithelial Cells Derived from MMTV-neu Mice Revealed that HER2/NEU-Driven Changes in Protein Expression Are Functionally Clustered

Abstract

MMTV-neu transgenic mice overexpressing NEU in their mammary glands develop tumor after 6 months of age. To find a novel protein biomarker using this mouse model, we identified and characterized the proteins that were differently expressed between primary mammary epithelial cells from 2 months old MMTV-neu heterozygote mice and wild type (WT) littermates using two-dimensional digest (ChemDigest (TM)/Trypsin)-LC-MS/MS. The differentially expressed proteins were selected and analyzed using DAVID Bioinformatics resource. The proteins involved in anti-apoptosis, purine metabolism, ribosome and proteasome functions were upregulated, whereas cell adhesion-related proteins were downregulated in PMECs from MMTV-neu mice when compared with WT PMECs. The results indicate that several functional units are coregulated by HER2/NEU. We hypothesize that these changes in the cellular proteome may be responsible for early onset of HER2/NEU-driven tumorigenesis.