GEO DataSets

(Submitter supplied) Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we have created genetically engineered mice with Brca1 loss and deletion of p16INK4A, or separately p18INK4C, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1 deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1 deficient breast cancers.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL2881 GPL10732

21 Samples

Download data: TXT

(Submitter supplied) TP53 is mutated in 50% of all cancers, and is often functionally compromised in cancers where it is not mutated. We demonstrate that the pro-tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism that does not involve the negative regulator of p53, MDM2. Instead, Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of the ribosomal protein L26 (RPL26), a positive regulator of p53 translation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

5 related Platforms

377 Samples

Download data

(Submitter supplied) Background: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models (GEMMs) are useful resources for studying breast cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and improve preclinical drug validation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

4 related Platforms

110 Samples

Download data

(Submitter supplied) Anticancer drug development is an inefficient process, with potential therapeutics demonstrating a high attrition rate due to lack of efficacy in Phase II/III testing. In an effort to develop improved pre-clinical predictors of efficacy, we and others have turned to testing in genetically engineered murine models (GEMMs) of cancer, which may offer some advantages to in vitro and xenograft systems. Specifically, we assessed the activity of 16 treatment regimens in a Ras-driven, Ink4a/Arf-deficient melanoma GEMM. Like human RAS-mutant melanoma, this GEMM was refractory to standard chemotherapy and single-agent small molecule therapies. Only one regimen exhibited significant anti-tumor activity in this model: combined treatment with AZD6244 (MEK inhibitor) and BEZ235 (dual PI3K/mTOR inhibitor), which produced marked tumor regression and improved survival. Given the surprising activity of the “AZD/BEZ” combination in a melanoma GEMM, we next tested this regimen in a Ras-driven orthotopic-transplant model of “claudin-low” breast cancer, which shares some gene expression features with melanoma. The AZD/BEZ regimen also exhibited significant activity in this related Ras-driven model, leading us to testing in even more diverse GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly active in each of these distinct breast models, demonstrating equal or greater efficacy compared to any other regimen tested in studies of over 700 tumor-bearing mice. This regimen even exhibited activity in tumors selected for resistance to another effective chemotherapy agent, lapatinib, in HER2+ models. These results demonstrate the utility of credentialed murine models for large-scale efficacy testing of diverse anti-cancer regimens, and predict combinations of PI3K/mTOR and MEK inhibitors will demonstrate anti-tumor activity in a wide-range of human malignancies.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL2881 GPL11383 GPL10732

16 Samples

Download data

(Submitter supplied) The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor initiating cells (TIC) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. more...

Organism:

Mus musculus

Type:

Expression profiling by array; Genome variation profiling by array; Genome variation profiling by genome tiling array

Platforms:

GPL10732 GPL4092 GPL4134

107 Samples

Download data

(Submitter supplied) Introduction: Over the past several years, we have been interested in understanding the mechanisms by which hormone-dependent (HD) mammary carcinomas grow in the absence of the stimulatory hormone. We have hypothesized that the stromal compartment plays a pivotal role in the acquisition of the hormone-independent (HI) phenotype by providing stimulatory factors that replace the proliferative effects of the hormone. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL2881 GPL10732

28 Samples

Download data

(Submitter supplied) agilent technology

Organism:

Mus musculus

6 Series

47 Samples

Download data