title: Pathway-based analysis of breast cancer.
abstract: BACKGROUND
  Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer.
  
  
  METHODS
  13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array.
  
  
  RESULTS
  Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways.
  
  
  CONCLUSIONS
  There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs.
authors.affiliation: Department of Breast Surgery, The First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine New York, NY 10029, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Breast Surgery, The First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Breast Surgery, The First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine New York, NY 10029, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Nolan
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine New York, NY 10029, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY 10010, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine New York, NY 10029, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine New York, NY 10029, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
keywords: Breast cancer; gene expression; protein abundance; signal transduction; signaling network