Expression data from AJ and C3H mouse lungs exposed to NNK
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: William Gordon
PROVIDER: E-GEOD-38952 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Identification of genes associated with exposure to the carcinogen Nitrosamine (NNK) in mouse lungs of susceptible (AJ) and resistant (C3H) strains. Microarrays were used to capture all of the up and down regulated genes in two strains of mice.
2012-09-01 | GSE38952 | GEO
Project description:The hepatocyte growth factor (HGF)/c-Met signaling pathway is known to mediate vascularization. We have previously demonstrated that expression of a human HGF transgene in the small airways produced mice (HGF TG) that were more susceptible to the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). We also have observed that HGF TG mice display significantly enhanced vascularization in the lungs that increases over time compared to wild-type (WT) littermates. To analyze which genes might contribute to increased vascularization from HGF overexpression in the airways, RNA and protein were isolated from whole lungs of individual HGF TG and WT adult mice. We profiled the mRNA expression of several hundred genes representative of six biological pathways involved in transformation, angiogenesis, and tumorigenesis using two commercial microarrays. Significant changes in expression over a 1.5-fold boundary were also observed in lung tumors derived from NNK-treated HGF TG mice. Lung tumors were induced by exposing mice to four weekly i.p. injections of 3mg NNK (15μg/μl) over 2 weeks. Whole lungs from control untreated animals were dissected after sacrifice at 10, 20, or 40 wks of age, and NNK induced lung tumors were dissected from the animals at 20 or 40 weeks of age. Total RNA was extracted from whole lung or isolated tumors from HGF TG or WT mice using TRIzol reagent and the Array Grade Total RNA Isolation Kit. The cDNA was generated and labeled using the TrueLabeling-AMP Linear RNA Amplication Kit. RNA was analyzed from 28 mice in total. The angiogenesis array was used to analyze 10 samples taken from 40 week old mice (HGF TG untreated [n=4], WT untreated [n=4], HGF TG NNK treated [n=1], WT NNK treated [n=1]) and 6 samples from 20 week old mice (HGF TG untreated [n=2], WT untreated [n=2], HGF TG NNK treated [n=1], WT NNK treated [n=1]). The cancer gene array was used to analyze 8 samples taken from 40 week old mice (HGF TG untreated [n=2], WT untreated [n=2], HGF TG NNK treated [n=2], WT NNK treated [n=2]) and 4 samples from 20 week old mice (HGF TG untreated [n=2], WT untreated [n=2]).
2010-12-31 | E-GEOD-20468 | biostudies-arrayexpress
Project description:This study evaluated transcriptional effects of the lung carcinogen NNK ( 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) injection and selenocystine consumption on the murine lung. Female A/J mice at 5 weeks of age were obtained from The Jackson Laboratory. Animals were stabilized on an unsupplemented AIN-76 diet for one week prior to being given the selenium supplemented diet. The basal level of selenium in the diet is 0.35 ppm Se, the selenocytine supplemention was at 15 ppm. NNK was administered i.p. as a single 10 uM injection in 0.2 mL saline. With this protocol, 100% of animals reproducibly develop lung tumors after 3 months. Three days after NNK administration, animals were provided AIN-76A diets supplemented with selenocystine at 15 ppm selenium ad libitum for 10 days. Animals were sacrificed thirteen days after NNK administration. Lung tissue was harvested, immediately homogenized in Trizol and frozen. The organic extracted RNAs were run over Qiagen RNeasy columes before quantifying and qualifying them. All samples had RNA quality index's greater than 9. Four groups of A/J mice were utilized with 4 biological replicates per group. 1) Untreated - controls on the AIN-76 diet (0.35 ppm Se). 2) NNK treated - single injection of NNK, maintained on norma AIN-76 diet, sacraficed after 13 days. 3) SECY - selenocystine supplemented (15 ppm) for 10 days on a AIN-76 diet then sacraficed. 4) NNK plus SECY - single injection of NNK, after 3 days, selenocystine supplemented (15 ppm) diet for 10 days then sacraficed. RNAs from the the four untreated mice were combined to phenotypically anchor the dual color expression profile. mouse lung responses to NNK injection and/or selenocystine dietary supplementation
2012-05-31 | E-GEOD-29447 | biostudies-arrayexpress
Project description:Purpose: Chronic pulmonary inflammation in the form of chronic obstructive pulmonary disease (COPD) has been consistently shown to increase the risk of lung cancer. Therefore, identification of chemopreventive agents with anti-inflammatory effects, in addition to antiproliferative and apoptotic activities, is indispensable. Recently, we found that combinations of silibinin (Sil) and indole-3-carbinol (I3C) significantly inhibited lung tumorigenesis induced by 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) and enhanced by chronic treatment with the inflammatory agent lipopolysaccharide (LPS). In this study, we described gene expression profiling of lung tissues using RNA-seq to determine the gene expression signature in inflammation-driven lung tumors and modulation of this signature by the chemopreventive agents Sil and I3C. Methods: Total RNA extracted from lung tissues of control and treated mice were processed for mRNA sequencing, in triplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed for transcript abundance at the gene level using CLC Bio Genomics Workbench and differential gene expression analysis was performed using the built-in Empirical Analysis of Differential Gene Expression (DGE) based on 'Exact Test' method. qRTâPCR validation was performed using SYBR Green assays. Results and conclusions: We found that 330, 2,957, and 1,143 genes were differentially regulated in mice treated with NNK, LPS, and NNK + LPS, respectively. The expression of inflammation-and immunity-related genes was significantly more deregulated in lung tissues of mice treated with LPS alone compared to mice treated with NNK + LPS. Among 1,143 genes differentially regulated in the NNK + LPS group, the expression of 162 genes and associated signaling pathways were significantly modulated by I3C and/or Sil + I3C. These genes include cytokines, chemokines, and genes with a well-established role in inflammation and/or tumorigenesis such as c-ros oncogene 1 (Ros1), the EGFR ligands amphiregulin and epiregulin, Cyp1a1, and the circadian rhythm genes Arntl, and Npas2. To our knowledge, this is the first report that provides insight into genes that are differentially expressed during inflammation-driven lung tumorigenesis and the modulation of these genes by chemopreventive agents. Lung tissue mRNA profiles of mice treated with control vehicle, NNK, LPS, NNK+LPS, or NNK+LPS supplemented with chemopreventive agent(s) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
2016-07-03 | E-GEOD-64027 | biostudies-arrayexpress
Project description:In order to assess the alteration in lncRNA expression in rat lung carcinogenesis induced by NNK, we determined the lncRNA expression profiles in 3 rat lung tumor samples and matched normal lung tissues and 2 blood samples from the control and NNK treatment group in the 95th week using Arraystar Rat lncRNA Microarray. We induced lung cancer using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in a rat model and determined the lncRNA expression profiles in lung cancer tissues and rat blood samples.
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Project description:Smoking perpetuates in cytologically-normal airways a molecular “field of injury” that is pertinent to lung cancer and early detection. The evolution of airway field changes prior to lung cancer onset is poorly understood largely due to the long latency of lung malignancy in smokers. Here we studied airway expression changes prior to lung cancer onset in mice with knockout of the Gprc5a gene and tobacco carcinogen (nicotine-specific nitrosamine ketone; NNK) exposure and that develop the most common type of lung cancer, lung adenocarcinoma (LUAD). Cytologically-normal airway epithelial brushings were collected before exposure and at multiple times following NNK exposure until time of LUAD development and then analyzed by RNA-sequencing (RNA-Seq).
2020-02-28 | GSE102707 | GEO
Project description:We have shown that Gprc5a-/- mice form Kras-mutant lung tumors spontaneously which is accelerated by tobacco carcinogen (NNK) exposure. We found in these mice that Lcn2 was distinctively up-regulated along the spectrum of Kras-mutant lung cancer development. To understand the role of Lcn2 in lung cancer pathogenesis, we generated Gprc5a-/-/Lcn2-/- mice and found that these animals have increased lung tumor devleopment following NNK compared to Gprc5a-/- animals with intact Lcn2. To understand these effects, we performed RNA-sequencing (RNA-Seq) of lung tissues from Gprc5a-/-/Lcn2-/- and Gprc5a-/- mice at baseline (prior to NNK exposure) and of tumor-bearing lungs from both groups at seven months post-NNK exposure.
2021-03-19 | GSE147148 | GEO
Project description:Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) in pancreatic intraepithelial neoplasm (PanIN) cells exposed to tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and to examine the upregulated pathways.
2018-09-06 | GSE119517 | GEO
Project description:Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we report that chimeric RNA RRM2-C2orf48 promotes 4-(methyl nitrosamine)-1-(3-pyridinyl)-1-butanone (NNK)-induced lung cancer. We found that RRM2-C2orf48 had higher expression levels in lung cancer cell lines and in lung cancer tissues from 74 patients than in normal cells and tissues, respectively. And its expression level was correlated with smoking. Next, we demonstrate that the expression level of RRM2-C2orf48 could increase after treatment with 200 mg/L NNK for 24 h. Overexpressing RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and promoted cell growth. Meanwhile, suppressing RRM2-C2orf48 inhibited cell growth. Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48. In summary, RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and miR-219a-2-3p may be involved in this process.
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