Project 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. Six spontaneous lung tumors and six normal lungs (as controls) from 2-year-old B6C3F1 mice.
Project 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.
Project description:To identify transcripts differentially expressed between control samples and spontaneous tumors, or control samples and antimony treated lung tumors, we collected RNA from male and female B6C3F1 mice from a 2-year inhalation NTP bioassay exposed to 0 to 30 mg/m3 antimony trioxide. These samples were interrogated with the Affymetrix Mouse Genome 430 2.0 GeneChip Array. A total of 9941 gene transcripts were differentially expressed between control samples and spontaneous tumors, and 12441 gene transcripts were differentially expressed between control samples and treated antimony tumors (false discovery rate (FDR) < 0.05).
Project description:To identify differentially expressed transcripts between control samples and spontaneous tumors, or control samples and cobalt treated tumors, we collected RNA from male and female B6C3F1 mice from a 2-year inhalation NTP bioassay exposed to 0 or 5 mg/m3 cobalt metal dust. These samples were interrogated with the Affymetrix Mouse Genome 430 2.0 GeneChip Array. A total of 11557 gene transcripts were differentially expressed between control samples and spontaneous tumors, and 12420 gene transcripts were differentially expressed between control samples and treated cobalt tumors (false discovery rate (FDR) < 0.05).
Project description:Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before. We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis. We analyzed the transcriptome, using the Affymetrix Human Gene 1.0 ST platform, of matched NSCLC tumors, multiple normal airway epithelia with differential distance from the tumors as well as uninvolved normal lung tissues. We analyzed the airway field cancerization transcritpome to determine global differentially expressed cancerization profiles in adjacent airways as well as airway profiles that may be modulated by distance from tumors.