Dataset Information


Affymetrix SNP array data for Trp53-null mammary tumors developed in a mouse model with a K8+ luminal cell origin

ABSTRACT: 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, including Basal-Like breast cancer (BLBC), might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CA(H1047R), 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 BLBCs, raising a question as to whether p53-loss plays a key role in acquisition of multipotent 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, due to increased cell cycle activity and attenuated apoptosis control, but did not directly affect their luminal identity. All induced mice eventually developed either Claudin-Low mammary tumors with 9qA1 (Yap1) amplification or Basal-Like tumors with 6qA1-A2 (Met) amplification. 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 tumors with loss of luminal identity. Overall design: Genomic DNAs from mammary tumors developed in Trp53L/L females 6-7 months after intraductal injection of Ad-K8-Cre adenovirus or from mammary glands of a strain background-matched wild-type female were prepared and subjected to mouse diversity SNP array analysis.

INSTRUMENT(S): [MOUSEDIVm520650] Affymetrix Mouse Diversity Genotyping Array


PROVIDER: GSE77497 | GEO | 2016-12-20



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Induced p53 loss in mouse luminal cells causes clonal expansion and development of mammary tumours.

Tao Luwei L   Xiang Dongxi D   Xie Ying Y   Bronson Roderick T RT   Li Zhe Z  

Nature communications 20170213

Most breast cancers may have a luminal origin. TP53 is one of the most frequently mutated genes in breast cancers. However, how p53 deficiency contributes to breast tumorigenesis from luminal cells remains elusive. Here we report that induced p53 loss in Krt8+ mammary luminal cells leads to their clonal expansion without directly affecting their luminal identity. All induced mice develop mammary tumours with 9qA1 (Yap1) and/or 6qA2 (Met) amplification(s). These tumours exhibit a mammary stem cel  ...[more]

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