Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-57133
PROVIDER: PRJNA203655 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1M-bM-^@M-^Ys expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer. Examination of genome-wide SMAD4 binding in 7-month-old Ptend/d mouse lung.
2015-03-05 | E-GEOD-57177 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer. knockout group (PTENd/d and SMAD4d/d) and control group
2015-03-12 | E-GEOD-47116 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer.
2015-03-12 | GSE47116 | GEO
Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1’s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
2015-03-05 | GSE57133 | GEO
Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1’s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
2015-03-05 | GSE57177 | GEO
Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1 expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer. The microarray data includes two different ages of mouse lung samples. The microarray for the study on late stage was did on 12-month-old wild type mouse lungs and Ptend/dSmad4d/d mouse lung tumors. This study was used to identify the significantly changed genes between lung tumors and wild type lungs. The microarray for the study on early stage was did on 7-month-old wild type, Ptend/d and Ptend/dSmad4d/d mouse lungs. This study was used to identify the significantly changed driven genes before the lung tumor initiation and metastasis.
2015-03-05 | E-GEOD-57133 | biostudies-arrayexpress
Project description:PB-Cre/Pten/Smad4 is a transgenic mouse model of metastatic prostate adenocarcinoma (PMID: 21289624). To study the transcriptomic alterations associated with castration-resistant prostate cancer (CRPC), the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. After about 4 weeks, dorsolateral prostate (DLP) lobes of treatment-naïve prostate tumors (N=2) and CRPC tumors (N=3) were harvested and extracted for RNA purification and microarray profiling. To further study the transcriptomic changes associated with lung metastases of the PB-Cre/Pten/Smad4/mTmG CRPC model, the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. About 3 months later, from one mouse anterior prostate (AP), dorsolateral prostate (DLP), ventral prostate (VP) and GFP+ lung metastasis nodules were each harvested for RNA purification and microarray profiling.
2020-12-18 | GSE163420 | GEO
Project description:Here we describe novel murine models of High Grade Neuroendocrine Lung Carcinomas driven by the loss of four tumor suppressors: deletion of Rb, PTEN, and p53, in a Rbl1 null background, in a wide variety of lung epithelial cells produces Large Cell Neuroendocrine Carcinoma whereas inactivation of these genes exclusively in basal cells leads to the development of Small Cell Lung Carcinoma, showing that Keratin K5 expressing cells contribute to the development/act as cell of origin of Small Cell Lung Carcinoma differentially influencing the lung cancer type developed. Conditional ablation of Rb1, Trp53 and Pten in pulmonary cells was achieved by intratracheal administration of purified Ad5-CMVcre or Ad5-K5cre (Du Page et al, 2009) to Rb1F/F;Trp53F/F;PtenF/F;Rbl1−/− 8–10 week old mice. Mice were sacrificed 3 to 5 months after the Ad5-cre infection and tumors processed for whole transcriptome analysis. As control animals, RbF/F;p53F/F;PtenF/F;Rbl1−/− littermates were used.
2019-10-15 | GSE121574 | GEO
Project description:ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that Erbb2 loss inhibited lung tumor development induced by deletion of Pten and Smad4. Transcriptome analysis showed that Erbb2 loss suppressed the significant changes of most of the induced genes by ablation of Pten and Smad4. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as MED24, during lung tumor development.
2019-06-19 | GSE128620 | GEO
Project description:The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Loss of SMAD4 is a key event in late-stage CRC resulting in the progression to metastatic CRC in 10-30% of the cases. However, the biological processes and underlying molecular mechanisms that it affects are not fully understood. Here, we applied a multi-omics approach to a CRC tumor progression organoid model that faithfully reflects the metastasis-inducing effects of SMAD4 inactivation. We show that loss of SMAD4 results in loss of differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFB, WNT, and VEGF pathways. In addition, SMAD4 inactivation leads to increased secretion of proteins that are known to be involved in a variety of pro-metastatic processes. Finally, we show that one of the factors that is specifically secreted by metastatic organoids – DKK3 – reduces the anti-tumor effects of natural killer cells (NKCs). Altogether, our data provides promising new targets concerning the role of SMAD4 perturbation and metastatic disease in CRC.
2022-12-11 | PXD036441 | Pride