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GSE26538
Mus musculus
12 Downloadable Samples
Description
Hepatocellular carcinoma (HCC) is an important cause of morbidity and mortality worldwide. Although the risk factors of human HCC are well known, the molecular characterization of this disease is complex, and treatment options in general remain poor. The use of rodent models to study human cancer has been extensively pursued both through genetically engineered rodents and rodent models used in carcinogenicity and toxicology studies. In particular, the B6C3F1 mouse used in the National Toxicology Program (NTP) 2-year bioassay has been used to evaluate the carcinogenic effects of environmental and occupational chemicals, and other compounds. The high incidence of spontaneous HCC in the B6C3F1 mouse has challenged its use as a model for chemically induced HCC in terms of relevance to the human disease. Using global gene expression profiling, we identify the dysregulation of several mediators similarly altered in human HCC, including re-expression of fetal oncogenes, upregulation of protooncogenes, downregulation of tumor suppressor genes, and abnormal expression of cell cycle mediators, growth factors, apoptosis regulators, and angiogenesis and extracellular matrix remodeling factors. Although important differences in etiology and pathogenesis remain between human and mouse HCC, there are important similarities in global gene expression and the types of signaling networks dysregulated in mouse and human HCC. These data provide further relevance for the use of this model in hazard identification of compounds with potential human carcinogenicity risk, and may help in better understanding mechanisms of tumorigenesis due to chemical exposure in the NTP 2-year carcinogenicity bioassay.
Publication Title
Global gene profiling of spontaneous hepatocellular carcinoma in B6C3F1 mice: similarities in the molecular landscape with human liver cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Introduction: Lung cancer is the leading cause of cancer-related death in people. There are several chemically induced and genetically modified mouse models used to study lung cancer. We hypothesized that spontaneous murine (B6C3F1) lung tumors can serve as a model to study human non-small cell lung cancer (NSCLC). Methods: RNA was extracted from untreated 2-year-old B6C3F1 mouse spontaneous lung (SL) tumors and age-matched normal lung tissue from a chronic inhalation NTP study. Global gene expression analysis was performed using Affymetrix Mouse Genome 430 2.0 GeneChip arrays. After data normalization, for each probe set, pairwise comparisons between groups were made using a bootstrap t-test while controlling the mixed directional false discovery rate (mdFDR) to generate a differential gene expression list. IPA, KEGG, and EASE software tools were used to evaluate the overrepresented cancer genes and pathways. Results: MAPK and TGF-beta pathways were overrepresented within the dataset. Almost all of the validated genes by quantitative real time RT-PCR had comparable directional fold changes with the microarray data. The candidate oncogenes included Kras, Braf, Raf1, Id2, Hmga1, Cks1b, and Foxf1. The candidate tumor suppressor genes included Rb1, Cdkn2a, Hnf4a, Tcf21, Ptprd, Hpgd, Hopx, Ogn, Id4, Hoxa5, Smad6, Smad7, Zbtb16, Cyr61, Dusp4, and Ifi16. In addition, several genes important in lung development were also differentially expressed, such as Smad6, Hopx, Sox4, Sox9 and Mycn. Conclusion: In this study, we have demonstrated that several cancer genes and signaling pathways relevant for human NSCLC were similarly altered in spontaneous murine lung tumors.
Publication Title
Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
Publication Title
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples