Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA222271 | ENA |
REPOSITORIES: ENA
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Project description:LKB1 is a tumor suppressor lost in approximately 30% of lung adenocarcinomas. It is a serine-threonine kinase involved in regulating metabolism, proliferation, and cell polarity. We have characterized its association with mRNA expression profiles in resected tumors and in cell lines, but little is known about the direct effects of LKB1 on the regulation of these genes. This study investigates the effects of LKB1 activity on mRNA expression in two LKB1-mutant lung adenocarcinoma cell lines, H2122 and A549. Wild-type LKB1 has been stably expressed in these cell lines using a pBABE retrovirus as well as an empty pBABE control and a kinase-dead mutant of LKB1 (K78I) control (Addgene). Samples submitted are two cell lines, three experimental conditions, and three replicates, for a total of 17 samples (one sample was excluded for poor RNA quality). Gene expression of these samples are analyzed to determine transcriptional regulatory effects of LKB1 expression. Results of this analysis are compared to our analysis of resected human tumors to determine gene patterns that are differentially expressed between LKB1-deficient and LKB1-wild-type tumors whose expression is also affected by restoration of LKB1 in vitro. RMA gene expression was taken from two cell lines stably expressing LKB1 or controls of K78I mutant LKB1 or empty pBABE vector. Log2 average expression differences are calculated and compared to results from analysis of gene expression associated with LKB1 loss in resected human tumors.
2013-10-01 | E-GEOD-51266 | biostudies-arrayexpress
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
2011-07-28 | E-TABM-1169 | biostudies-arrayexpress
Project description:LKB1 is a tumor suppressor lost in approximately 30% of lung adenocarcinomas. It is a serine-threonine kinase involved in regulating metabolism, proliferation, and cell polarity. We have characterized its association with mRNA expression profiles in resected tumors and in cell lines, but little is known about the direct effects of LKB1 on the regulation of these genes. This study investigates the effects of LKB1 activity on mRNA expression in two LKB1-mutant lung adenocarcinoma cell lines, H2122 and A549. Wild-type LKB1 has been stably expressed in these cell lines using a pBABE retrovirus as well as an empty pBABE control and a kinase-dead mutant of LKB1 (K78I) control (Addgene). Samples submitted are two cell lines, three experimental conditions, and three replicates, for a total of 17 samples (one sample was excluded for poor RNA quality). Gene expression of these samples are analyzed to determine transcriptional regulatory effects of LKB1 expression. Results of this analysis are compared to our analysis of resected human tumors to determine gene patterns that are differentially expressed between LKB1-deficient and LKB1-wild-type tumors whose expression is also affected by restoration of LKB1 in vitro.
2013-10-01 | GSE51266 | GEO
Project description:Background: LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. Restoration of Lkb1 in established lung tumors promotes the expression of C/EBP target genes as well as features of alveolar type II cell differentiation, which requires the activity of C/EBP transcription factors in the developmental setting. Purpose: To determine the extent to which the disruption of C/EBP transcription factors recapitulates the transcriptional changes induced by the inactivation of Lkb1.Approach: To assess the changes gene expression induced by CRISPR/Cas9-mediated disruption of either C/EBP transcription factors or Lkb1, we induced lung tumors in KrasLSL-G12D/+;R26LSL-tdTomato;H11LSL-Cas9 mice using Lenti-sgNeo1/sgNT/sgNeo2/Cre (sgInert), Lenti-sgLkb1/Cre (sgLkb1), or Lenti-sgCebpa/sgCebpb/sgCebpd/Cre (sgCebpa/b/d). Neoplastic cells were then isolated from lung tumors by FACS for gene expression profiling by RNA-seq. Results: The disruption of C/EBP transcription factors partially recapitulates the gene expression changes induced by Lkb1 inactivation. Among the genes that are jointly dependent upon C/EBP transcription factors and LKB1 is an enrichment of NKX2-1-dependent target genes. Conclusions: C/EBP transcription factors likely operate downstream of LKB1 in an indirect manner, collaborating with another key developmental regulator, NKX2-1, to enforce alveolar type II cell differentiation to constrain tumor growth.
2021-12-23 | GSE179558 | GEO
Project description:NKX2-1 occupancy in human lung adenocarcinoma cell lines
| PRJNA172254 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Global transcriptional profiling changes upon knockdown of LKB1 in human glioblastoma cell lines
| PRJNA356645 | ENA
Project description:LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. To identify the processes governed by LKB1 in vivo, we generated an allele which enables Lkb1 inactivation during tumor development and subsequent Lkb1 restoration in established tumors. Restoration of Lkb1 in oncogenic KRAS-driven lung tumors suppressed proliferation and promoted tumor stasis. Lkb1 restoration activated targets of C/EBP transcription factors and drove the transition of neoplastic cells from a progenitor-like state to a less proliferative alveolar type II cell-like state. We show that C/EBP transcription factors govern a subset of genes that are induced by LKB1 and depend upon NKX2-1. We also demonstrate that a defining factor of the alveolar type II lineage, C/EBPα, constrains oncogenic KRAS-driven lung tumor growth. Thus, we uncover a role for a critical tumor suppressor in the regulation of key lineage-specific transcription factors, thereby constraining lung tumor development through the enforcement of differentiation.
2021-12-23 | PXD026738 | Pride
Project description:Identification of ZEB1-regulated gene expression changes in HCC827 human lung adenocarcinoma cells
| PRJNA320768 | ENA