Reference SummaryLi Z, Cancer Cell 2007 Dec;12(6):542-58
Title |
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. |
Authors |
Li Z; Tognon CE; Godinho FJ; Yasaitis L; Hock H; Herschkowitz JI; Lannon CL; Cho E; Kim SJ; Bronson RT; Perou CM; Sorensen PH; Orkin SH |
Journal |
Cancer Cell |
Volume |
12 |
Issue |
6 |
Year |
2007 |
Pages |
542-58 |
Abstract |
To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61(+) luminal progenitors are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models. |
Links |
J:130323 – MGI References 18068631 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| [not specified]-Gt(ROSA)26Sortm1Sho Tg(Wap-cre)11738Mam | Mammary gland hyperplasia | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-cre)11738Mam | Mammary gland hyperplasia - alveolar | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Gt(ROSA)26Sortm1Sho Tg(Wap-cre)11738Mam | Mammary gland hyperplasia - alveolar | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-cre)11738Mam | Mammary gland hyperplasia - lobular-alveolar | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-cre)11738Mam | Mammary gland metaplasia - squamous | Mammary gland |
observed |
||
| [not specified]-Gt(ROSA)26Sortm1Sho Tg(Wap-cre)11738Mam | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ | Mammary gland tumor | Mammary gland |
observed - sporadic |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-cre)11738Mam | Mammary gland tumor | Mammary gland |
40 - 100 |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Gt(ROSA)26Sortm1Sho Tg(Wap-cre)11738Mam | Mammary gland tumor | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-rtTA-cre)10Whl | Mammary gland tumor | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Gt(ROSA)26Sortm1(Luc)Kael Tg(Wap-rtTA-cre)10Whl | Mammary gland tumor | Mammary gland |
observed |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(MMTV-cre)FMam | (Unspecified organ) lesion | (Unspecified organ) |
very high |