The Role of Lkb1 in Mouse Lung Squamous Cell Carcinoma (SCC) Development
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ABSTRACT:
PROVIDER: PRJNA436645 | ENA |
REPOSITORIES: ENA
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Project description:Lung cancer, majorly divided into non-small cell lung cancer (80-85%) and small cell lung cancer (15-20%), is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of major subtypes of non-small cell lung cancer. Although genomic analysis of tumors from SSC patients have identified frequently mutated genes in these tumors, it’s still largely unknown which genes determine SCC development. Now we found that ablation of alone Lkb1 could induce SCC around 12 months of age. Therefore, transcriptome analysis of lung SCC of CCSPiCreLkb1f/f mice will help us understand how Lkb1 regulates the development of lung SCC.
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Project description:Lung cancer is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of the subtypes of lung cancer. It is still largely unknown which genes or pathways regulate lung SCC development. Recently, we found JNK1/2 pathway was inhibited in mouse lung SCC induced by double ablation of Pten and Lkb1 in mouse lung epithelial cells. Now we aim to identify a genome-wide molecular signature of JNK1/2 signaling in mouse squamous cell carcinoma cells and determine pathways that transduce JNK1/2 signaling.
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Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells. Kras tumor stroma cells and LP tumor stroma cells were sorted by FACS, the cells were gated as EpCAM-/CD45+/CD31+
2014-01-24 | E-GEOD-54352 | biostudies-arrayexpress
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells. Normal EpCAM+, Kras tumor EpCAM+ and LP tumor EpCAM+ were sorted by FACS, the cells were gating as EpCAM+/CD45-/CD31-
2014-01-24 | E-GEOD-54351 | biostudies-arrayexpress
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells.
2014-01-24 | GSE54351 | GEO
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells.
2014-01-24 | GSE54352 | GEO
Project description:Lung cancer, majorly divided into non-small cell lung cancer (80-85%) and small cell lung cancer (15-20%), is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of major subtypes of non-small cell lung cancer. Although genomic analysis of tumors from SSC patients have identified frequently mutated genes in these tumors, it’s still largely unknown which genes determine SCC development. Now we found that ablation of Lkb1 and Pten could induce SCC and ASC around 3 months of age. Therefore, transcriptome analysis of lung SCC and ASC of CCSPiCreLkb1f/f mice will help us understand how Lkb1 and Pten regulate the development of lung SCC and ASC.
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Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2 Profiling of 26 advanced (stage III) lung SCC. Replicates : each tumor sample is hybridized together with a normal dna sample to one microarray. Each microarray contain 3 replicates per BAC clone.
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Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2
2010-02-10 | GSE14859 | GEO
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. Chromosome 3 aberrations are indeed among the most frequent alterations in lung SCC and correlate with SCC patient's poor prognosis. We have precisely mapped regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC (GSE14859) amd moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. These amplicons were precisely mapped in these tumors using arraCGH with a 3q26.3 dedicated tiling array. Keywords : ArrayCGH, lung Squamous Cell Carcinoma, 3q26.3, SOX2 Keywords: ArrayCGH Profiling of 5 advanced (stage III) lung SCC using a chromosome 3 array providing 3q26.3-q27 tiling coverage. Replicates : each array contains three replicates per clone and each sample is hybridized to two arrays, results are subsequently averaged.
2010-02-09 | E-GEOD-15079 | biostudies-arrayexpress