Genome wide proteomics of ERBB2 and EGFR and other oncogenic pathways in inflammatory breast cancer

摘要: In this study we selected three breast cancer cell lines (SKBR3, SUM149 and SUM190) with different oncogene expression levels involved in ERBB2 EGFR signaling pathways as a model system for the evaluation of selective integration subsets transcriptomic proteomic data. We assessed status reads per kilobase million mapped (RPKM) values (14.4, 400, 300 SUM149, SUM190, SKBR3, respectively) (60.1, not detected, 1.4 same 3 lines). then used RNA-Seq data to identify those oncogenes significant transcript these (total 31) interrogated corresponding proteomics sets proteins interaction oncogenes. The number observed interactors each showed range, e.g., 4.2% (JAK1) 27.3% (MYC). percentage is measured fraction total protein interactions given set vs that STRING (Search Tool Retrieval Interacting Genes/Proteins, version 9.0) I2D (Interologous Interaction Database, 1.95). This approach allowed us focus on 4 main oncogenes, ERBB2, EGFR, MYC, GRB2, pathway analysis. bioinformatics sites GeneGo, PathwayCommons NCI receptor networks contained four had good coverage well interactors. identified were ERBB signaling, EGFR1 integrin outside-in validated targets C-MYC transcriptional activation. greater dynamic range use ratios correlate relative transcripts pathways. provided potential signatures 190 lines, growth factor receptor-bound 7 (GRB7), Crk-like (CRKL) Catenin delta-1 (CTNND1) signaling; caveolin 1 (CAV1), plectin (PLEC) filamin A (FLNA) actinin alpha1 (ACTN1) (associated high transcript) signalings; branched chain amino-acid transaminase (BCAT1), carbamoyl-phosphate synthetase (CAD), nucleolin (NCL) (high transcript); transferrin (TFRC), metadherin (MTDH) MYC S100-A2 (S100A2), Serpin B5 (SERPINB5), stratifin (SFN), PYD CARD domain containing (PYCARD), EPH A2 (EPHA2) PI3K p53 subpathway. Future studies inflammatory (IBC), from which derived, will be explore significance observations.