Reference SummaryAndrechek ER, Proc Natl Acad Sci U S A 2009 Sep 22;106(38):16387-92
Title |
Genetic heterogeneity of Myc-induced mammary tumors reflecting diverse phenotypes including metastatic potential. | ||||||
Authors |
Andrechek ER; Cardiff RD; Chang JT; Gatza ML; Acharya CR; Potti A; Nevins JR | ||||||
Journal |
Proc Natl Acad Sci U S A | ||||||
Volume |
106 | ||||||
Issue |
38 | ||||||
Year |
2009 | ||||||
Pages |
16387-92 | ||||||
Abstract |
Human cancers result from a complex series of genetic alterations, resulting in heterogeneous disease states. Dissecting this heterogeneity is critical for understanding underlying mechanisms and providing opportunities for therapeutics matching the complexity. Mouse models of cancer have generally been used to reduce this complexity and focus on the role of single genes. Nevertheless, our analysis of tumors arising in the MMTV-Myc model of mammary carcinogenesis reveals substantial heterogeneity, seen in both histological and expression phenotypes. One contribution to this heterogeneity is the substantial frequency of activating Ras mutations. Additionally, we show that these Myc-induced mammary tumors exhibit even greater heterogeneity, revealed by distinct histological subtypes as well as distinct patterns of gene expression, than many other mouse models of tumorigenesis. Two of the major histological subtypes are characterized by differential patterns of cellular signaling pathways, including beta-catenin and Stat3 activities. We also demonstrate that one of the MMTV-Myc mammary tumor subgroups exhibits metastatic capacity and that the signature derived from the subgroup can predict metastatic potential of human breast cancer. Together, these data reveal that a combination of histological and genomic analyses can uncover substantial heterogeneity in mammary tumor formation and therefore highlight aspects of tumor phenotype not evident in the population as a whole. | ||||||
Links |
J:153233 – MGI References 19805309 – National Library of Medicine/PubMed |
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Strain Notes
|
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| BALB/cJ-Brca1tm1Bhk/+ Trp53tm1Tyj/+ | Mammary gland carcinoma |
|
Mammary gland |
observed |
|
| BALB/cJ-Trp53tm1Tyj/+ | Mammary gland carcinoma |
|
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 |
|
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 |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Erbb2*)NDL2-5Mul | Mammary gland tumor | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - EMT | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - EMT | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - microacinar | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - microacinar | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - mixed | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - mixed | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - papillary | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - papillary | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - solid | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - solid | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc)WT#Jrn | Mammary gland tumor - squamous | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Myc*T58A)TA#Jrn | Mammary gland tumor - squamous | Mammary gland |
observed |