title: Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.
abstract: BACKGROUND
  Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.
  
  
  RESULTS
  Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors.
  
  
  CONCLUSIONS
  Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.
authors.affiliation: Lineberger Comprehensive Cancer Center. jih@unc.edu
authors.forename: Jason I
authors.initials: JI
authors.lastname: Herschkowitz
authors.forename: Karl
authors.initials: K
authors.lastname: Simin
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Weigman
authors.forename: Igor
authors.initials: I
authors.lastname: Mikaelian
authors.forename: Jerry
authors.initials: J
authors.lastname: Usary
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.forename: Karen E
authors.initials: KE
authors.lastname: Rasmussen
authors.forename: Laundette P
authors.initials: LP
authors.lastname: Jones
authors.forename: Shahin
authors.initials: S
authors.lastname: Assefnia
authors.forename: Subhashini
authors.initials: S
authors.lastname: Chandrasekharan
authors.forename: Michael G
authors.initials: MG
authors.lastname: Backlund
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Yin
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Khramtsov
authors.forename: Roy
authors.initials: R
authors.lastname: Bastein
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Robert I
authors.initials: RI
authors.lastname: Glazer
authors.forename: Powel H
authors.initials: PH
authors.lastname: Brown
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Green
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Furth
authors.forename: Juan P
authors.initials: JP
authors.lastname: Palazzo
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bernard
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
authors.forename: Terry
authors.initials: T
authors.lastname: Van Dyke
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity
chemical_list: D009363:Neoplasm Proteins