Reference SummaryBultman SJ, Oncogene 2008 Jan 17;27(4):460-8
Title |
Characterization of mammary tumors from Brg1 heterozygous mice. | ||||||||
Authors |
Bultman SJ; Herschkowitz JI; Godfrey V; Gebuhr TC; Yaniv M; Perou CM; Magnuson T | ||||||||
Journal |
Oncogene | ||||||||
Volume |
27 | ||||||||
Issue |
4 | ||||||||
Year |
2008 | ||||||||
Pages |
460-8 | ||||||||
Abstract |
Mammalian SWI/SNF-related complexes have been implicated in cancer based on some of the subunits physically interacting with retinoblastoma (RB) and other proteins involved in carcinogenesis. Additionally, several subunits are mutated or not expressed in tumor-derived cell lines. Strong evidence for a role in tumorigenesis in vivo, however, has been limited to SNF5 mutations that result primarily in malignant rhabdoid tumors (MRTs) in humans and MRTs as well as other sarcomas in mice. We previously generated a null mutation of the Brg1 catalytic subunit in the mouse and reported that homozygotes die during embryogenesis. Here, we demonstrate that Brg1 heterozygotes are susceptible to mammary tumors that are fundamentally different than Snf5 tumors. First, mammary tumors are carcinomas not sarcomas. Second, Brg1+/- tumors arise because of haploinsufficiency rather than loss of heterozygosity. Third, Brg1+/- tumors exhibit genomic instability but not polyploidy based on array comparative genomic hybridization results. We monitored Brg1+/-, Brm-/- double-mutant mice but did not observe any tumors resembling those from Snf5 mutants, indicating that the Brg1+/- and Snf5+/- tumor phenotypes do not differ simply because Brg1 has a closely related paralog whereas Snf5 does not. These findings demonstrate that BRG1 and SNF5 are not functionally equivalent but protect against cancer in different ways. We also demonstrate that Brg1+/- mammary tumors have relatively heterogeneous gene expression profiles with similarities and differences compared to other mouse models of breast cancer. The Brg1+/- expression profiles are not particularly similar to mammary tumors from Wap-T121 transgenic line where RB is perturbed. We were also unable to detect a genetic interaction between the Brg1+/- and Rb+/- tumor phenotypes. These latter findings do not support a BRG1-RB interaction in vivo. | ||||||||
Links |
J:132091 – MGI References 17637742 – National Library of Medicine/PubMed |
||||||||
Strain Notes
|
|||||||||
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| STOCK Smarca2tm1Mya Smarca4tm1Mag/+ | Blood vessel hemangiosarcoma | Blood vessel |
observed |
||
| STOCK Smarca4tm1Mag/+ | Bone osteosarcoma | Subcutis |
0.8 - 2.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland adenocarcinoma | Mammary gland |
2.2 - 8.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland adenocarcinoma - trabecular | Mammary gland |
0.8 - 1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland adenocarcinoma - trabecular/papillary | Mammary gland |
2.2 - 2.4 |
||
| 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 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma | Mammary gland |
8.5 - 11.8 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma | Blood vessel |
observed |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - small cuboidal | Mammary gland |
0.8 - 1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - trabecular | Mammary gland |
0.8 - 1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - well-differentiated | Mammary gland |
0.8 - 1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland metaplasia - squamous | Mammary gland |
3.1 - 4.7 |
||
| BALB/cJ | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| FVB/NJ | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| STOCK Smarca2tm1Mya Smarca4tm1Mag/+ | Mammary gland tumor | Mammary gland |
observed |
||
| STOCK Rb1tm1Tyj/+ | Pituitary gland tumor | Pituitary gland |
100 |
||
| STOCK Rb1tm1Tyj/+ Smarca4tm1Mag/+ | Pituitary gland tumor | Pituitary gland |
100 |
||
| STOCK Smarca4tm1Mag/+ | (Unspecified organ) tumor | (Unspecified organ) |
4.4 - 11.8 |
||
| STOCK | (Unspecified organ) tumor | (Unspecified organ) |
0 |
||
| STOCK Smarca2tm1Mya Smarca4tm1Mag/+ | (Unspecified organ) tumor | (Unspecified organ) |
10 |
||
| STOCK Smarca4tm1Mag/+ | (Unspecified organ) tumor - rhabdoid - malignant | (Unspecified organ) |
0 |
||
| STOCK Smarca2tm1Mya Smarca4tm1Mag/+ | (Unspecified organ) tumor - rhabdoid - malignant | (Unspecified organ) |
0 |