Reference SummaryHerschkowitz JI, Genome Biol 2007;8(5):R76

Title

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

Authors

Herschkowitz JI; Simin K; Weigman VJ; Mikaelian I; Usary J; Hu Z; Rasmussen KE; Jones LP; Assefnia S; Chandrasekharan S; Backlund MG; Yin Y; Khramtsov AI; Bastein R; Quackenbush J; Glazer RI; Brown PH; Green JE; Kopelovich L; Furth PA; Palazzo JP; Olopade OI; Bernard PS; Churchill GA; Van Dyke T; Perou CM

Journal

Genome Biol

Volume

8

Issue

5

Year

2007

Pages

R76

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. CONCLUSION: 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.

Links

17493263 – National Library of Medicine/PubMed

Strain Notes

Strain Note
BALB/cJ-Brca1tm1Bhk/+ Trp53tm1Tyj/+ The reference did not indicate if these mice were simply a product of crossing single KO congenic strains or if the double KO mice were subsequently fully backcrossed onto BALB/cJ. The strain name assumes that they are the product of a cross without backcrossing.
BALB/cJ-Trp53tm1Tyj/+ The reference did not indicate if these mice were simply a product of crossing single KO congenic strains or if the double KO mice were subsequently fully backcrossed onto BALB/cJ or if they were the single KO congenic mice. The strain name assumes that they are the product of a cross without backcrossing.
C57BL/6-Brca1tm2Cxd Trp53tm1Brd/+ Tg(MMTV-cre)4Mam Most of the data from the reference and supplemental info indicates that the Brca1 alleles were Brca1tm2Cxd/Brca1tm2Cxd but one column in a supplemental table stated that they were Brca1tm1Cxd/Brca1tm2Cxd. The former is assumed to be correct.
FVB.Cg-Tg(Wnt1)1Hev These mice had been backcrossed onto FVB.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
BALB/cJ-Brca1tm1Bhk/+ Trp53tm1Tyj/+ Mammary gland carcinoma
  • gamma-radiation
Mammary gland

observed

BALB/cJ-Trp53tm1Tyj/+ Mammary gland carcinoma
  • gamma-radiation
Mammary gland

observed

C.Cg-Tg(WAPT121)66Tvd Mammary gland carcinoma Mammary gland

observed

B6D2-Tg(WAPT121)66Tvd Mammary gland carcinoma Mammary gland

observed

C57BL/6J-Tg(WapTAg)1Knw Mammary gland carcinoma Mammary gland

observed

C57BL/6-Brca1tm2Cxd Trp53tm1Brd/+ Tg(MMTV-cre)4Mam Mammary gland carcinoma Mammary gland

observed

FVB Mammary gland carcinoma
  • medroxyprogesterone actetate (MPA)
  • dimethylbenzanthracene (DMBA)
Mammary gland

observed

FVB-Tg(C3-1-TAg)cJeg Mammary gland carcinoma Mammary gland

observed

FVB-Tg(MMTVneu)202Mul Mammary gland carcinoma Mammary gland

observed

FVB-Tg(MMTV-PyVT)634Mul Mammary gland carcinoma Mammary gland

observed

FVB.Cg-Tg(Wnt1)1Hev Mammary gland carcinoma Mammary gland

observed

FVB-Tg(WapNotch4)10Rnc Mammary gland carcinoma Mammary gland

observed

FVB.Cg-Tg(WapMyc)212Bri Mammary gland carcinoma Mammary gland

observed

BALB/cJ Mammary gland normal tissue (control) Mammary gland

not applicable

FVB/NJ Mammary gland normal tissue (control) Mammary gland

not applicable