Reference SummaryJiang Z, J Clin Invest 2010 Sep 1;120(9):3296-309
Title |
Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. | ||||||||||
Authors |
Jiang Z; Deng T; Jones R; Li H; Herschkowitz JI; Liu JC; Weigman VJ; Tsao MS; Lane TF; Perou CM; Zacksenhaus E | ||||||||||
Journal |
J Clin Invest | ||||||||||
Volume |
120 | ||||||||||
Issue |
9 | ||||||||||
Year |
2010 | ||||||||||
Pages |
3296-309 | ||||||||||
Abstract |
Breast cancer is a highly heterogeneous disease, with several different subtypes being characterized by distinct histology, gene expression patterns, and genetic alterations. The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost in both luminal-B and triple-negative tumor (TNT; i.e., estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative) breast cancer subtypes. However, a causal role for RB1 loss in different subtypes remains undefined. Here we report that deletion of Rb alone or together with its relative p107 in mouse mammary stem/bipotent progenitor cells induced focal acinar hyperplasia with squamous metaplasia. These lesions progressed into histologically diverse, transplantable mammary tumors with features of either luminal-B or TNT subtypes. The TNTs included basal-like tumors as well as tumors that exhibited epithelial-to-mesenchymal transition (EMT). The EMT-type tumors and a subset of the basal-like tumors, but not luminal-B-like tumors, expressed mutant forms of the tumor suppressor p53. Accordingly, targeted deletion of both Rb and p53 in stem/bipotent progenitors led to histologically uniform, aggressive, EMT-type tumors. Reintroduction of Rb into these tumor cells suppressed growth in vitro and tumor formation in vivo. These results establish a causal role for Rb loss in breast cancer in mice and demonstrate that cooperating oncogenic events, such as mutations in p53, dictate tumor subtype after Rb inactivation. | ||||||||||
Links |
J:165289 – MGI References 20679727 – 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 |
|---|---|---|---|---|---|
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - cystic | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - poorly differentiated | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(Wap-cre)11738Mam | Mammary gland adenocarcinoma - solid | Mammary gland |
very low |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - solid | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - solid/nodular | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - squamous | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - squamous | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenomyoepithelioma - papillary | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland carcinoma - acinar | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland carcinoma - adenosquamous | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland carcinoma - microacinar | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Tg(MMTV-cre)#Tfln | Mammary gland hyperplasia | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland hyperplasia | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland hyperplasia | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland keratoacanthoma - squamous | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland keratoacanthoma - squamous | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(Wap-cre)11738Mam | Mammary gland tumor | Mammary gland |
0 |
||
| [not specified]-Rb1tm2Brn Tg(MMTV-cre)#Tfln | Mammary gland tumor | Mammary gland |
100 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland tumor | Mammary gland |
100 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland tumor | Mammary gland |
100 |
||
| [not specified]-Rb1tm2Brn | Mammary gland tumor | Mammary gland |
0 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ | Mammary gland tumor | Mammary gland |
0 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj | Mammary gland tumor | Mammary gland |
0 |
||
| [not specified]-Rb1tm2Brn Tg(MMTV-cre)4Mam | Mammary gland tumor | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)4Mam | Mammary gland tumor | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn/+ Rbl1tm1Tyj/+ Tg(MMTV-cre)4Mam | Mammary gland tumor | Mammary gland |
observed |