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.
Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer.
Disease, Disease stage
View SamplesIdentification of the counterpart protein of Nef during HIV infection
HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation.
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View SamplesPAR-1 is known to be involved in the transition from non-metastatic to metastatic melanoma. We sought to determine the downstream target genes regulated by PAR-1 to determine how PAR-1 is contributing to the metastatic melanoma phenotype.
Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype.
Specimen part, Cell line
View SamplesMolecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury
Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury.
Specimen part, Disease, Time
View SamplesHuman testicular cells were isolated mechanically and enzymatically from testis of braindead donors and from urological samples. The expression of genes was studied at baseline and 1,25(OH)2D treated conditions.
Testicular synthesis and vitamin D action.
Specimen part
View SamplesInterleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome wide association studies and experimental animal models point at a central role of the IL-10 axis in Inflammatory Bowel Diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10R) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1hi-expressingmacrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages, but resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning factor in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation.
Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.
Age, Specimen part
View SamplesLy6Chi monocytes massively infiltrate the CRC-tumors by virtue of their CCR2 expression and further mature into Ly6CloF4/80hi CD64hiMHCII+ TAM upon tumor progression. We demonstrated that TAM-deficient tumors display impaired tumor-growth via alternation of the ECM morphology, structure and composition. Using advanced high-resolution optical imaging to visualize the tumoral-ECM macromolecule network together with transcriptomic and proteomic approaches we unraveled that TAM play critical role in the deposition, linearization and cross-linking of collagenous ECM. Remarkably, we show that cues embedded in ECM by TAM-mediated remodeling activity promote tumor cell proliferation in vitro and orthotopic tumor development in vivo.
Tumor macrophages are pivotal constructors of tumor collagenous matrix.
Sex, Specimen part
View SamplesWe showed different function of monocyte derived cells in the lamina propria of the colon under steady state and inflammatory conditions.
Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells.
Sex, Specimen part
View SamplesStudy the role of klotho as a tumor suppressor in colorectal cancer.
Klotho suppresses colorectal cancer through modulation of the unfolded protein response.
Cell line
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