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| Status |
Public on Dec 20, 2016 |
| Title |
Microarray expression profiling data for Trp53-null mammary epithelial cells and tumors from a mouse model with a K8+ luminal cell origin |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mammary epithelium is hierarchically organized, with multipotent basal mammary stem cells (MaSCs) producing both luminal and basal cells during development or upon transplantation. Recent studies suggested that most breast cancers might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CAH1047R, could induce multipotency in committed luminal cells. p53 is the most commonly mutated gene in human breast cancer; in particular, its inactivating mutations are found in most triple-negative breast cancers, raising a question as to whether p53-loss plays a key role in acquisition of MaSC-like properties by luminal cells. By in situ lineage tracing, we found that induced loss of p53 in Keratin 8 (K8)+ luminal cells led to their clonal expansion, in part due to increased proliferation, but did not directly affect their luminal identity. Expansion of luminal cells, in particular oestrogen receptor-positive luminal cells, was observed 3-4 weeks after induced p53-loss, which was accompanied by increased expression of cell cycle genes and downregulation of genes related to immune microenvironment, p53 downstream pathway and apoptosis control. All induced mice eventually developed mammary tumours with 9qA1 (Yap1) amplification and/or 6qA2 (Met) amplification. The resulting tumours exhibited a MaSC-like expression signature and most closely resembled Claudin-Low breast cancer. Overall, these data suggest that although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumours with loss of luminal identity. Our data also suggest that Claudin-Low breast cancer can originate from luminal cells, possibly upon transition through a basal-like state.
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| Overall design |
Total RNAs from YFP+ mammary epithelial cells sorted from K8-CreER;Trp53L/L;Rosa26-Stop-YFP or K8-CreER;Rosa26-Stop-YFP females 4 weeks after tamoxifen induction, or from mammary tumors developed in Trp53L/L females or K8-CreER;Trp53L/L females 6-7 months after intraductal injection of Ad-K8-Cre adenovirus or tamoxifen induction, respectively, were prepared and subjected to microarray expression profiling.
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| Contributor(s) |
Xie Y, Tao L, Li Z |
| Citation(s) |
28194015 |
| Submission date |
Feb 02, 2016 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Zhe Li |
| E-mail(s) |
zli4@rics.bwh.harvard.edu
|
| Organization name |
Brigham and Women's Hospital
|
| Department |
Medicine, Genetics Division
|
| Lab |
Li Lab
|
| Street address |
77 Avenue Louis Pasteur, Room 466
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (16)
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| GSM2228827 |
Normal YFP+ K8+ luminal mammary epithelial cells from TC143 |
| GSM2228828 |
Normal YFP+ K8+ luminal mammary epithelial cells from TC189 |
| GSM2228829 |
Normal YFP+ K8+ luminal mammary epithelial cells from TC190 |
| GSM2228830 |
Trp53-null YFP+ K8+ luminal mammary epithelial cells from TC201 |
| GSM2228831 |
Trp53-null YFP+ K8+ luminal mammary epithelial cells from TC204 |
| GSM2228832 |
Trp53-null YFP+ K8+ luminal mammary epithelial cells from TC213 |
| GSM2228833 |
Trp53-null YFP+ K8+ luminal mammary epithelial cells from TC258 |
| GSM2228834 |
Trp53-null mammary tumor developed in mouse E2 |
| GSM2228835 |
Trp53-null mammary tumor developed in mouse E4 |
| GSM2228836 |
Trp53-null mammary tumor developed in mouse E5 |
| GSM2228837 |
Trp53-null mammary tumor developed in mouse E7 |
| GSM2228838 |
Trp53-null mammary tumor developed in mouse E8 |
| GSM2228839 |
Trp53-null mammary tumor developed in mouse E9 |
| GSM2357555 |
Trp53-null mammary tumor developed in mouse TB208 |
| GSM2357556 |
Trp53-null mammary tumor developed in mouse TB209 |
| GSM2357557 |
Trp53-null mammary tumor developed in mouse TB239 |
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| This SubSeries is part of SuperSeries: |
| GSE77498 |
Induced loss of p53 in mammary luminal cells leads to their clonal expansion and facilitates development of mammary tumours with loss of luminal identity |
|
| Relations |
| BioProject |
PRJNA310637 |
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