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Analysis of Nkx2-1-regulated gene expression in A549 lung carcinoma cells

ABSTRACT: A transcription factor Nkx2-1 (also known as TTF-1) regulates the expression of different sets of genes. Gene expression analysis was performed using mRNAs from Nkx2-1-induced A549 cells compared to that from the control A549 cells. We used microarrays to detail the global program of gene expression controlled by Nkx2-1 and identified distinct classes of up-regulated and down-regulated genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40584 | GEO | 2012/09/05

SECONDARY ACCESSION(S): PRJNA174347

REPOSITORIES: GEO

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Analysis of Nkx2-1-regulated gene expression in A549 lung carcinoma cells

Project description:A transcription factor Nkx2-1 (also known as TTF-1) regulates the expression of different sets of genes. Gene expression analysis was performed using mRNAs from Nkx2-1-induced A549 cells compared to that from the control A549 cells. We used microarrays to detail the global program of gene expression controlled by Nkx2-1 and identified distinct classes of up-regulated and down-regulated genes. mRNAs were isolated from control and Nkx2-1-induced A549 cells and hybridized on Affymetrix microarrays. We sought to identify genes influenced by Nkx2-1.

2012-09-05 | E-GEOD-40584 | biostudies-arrayexpress

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2014-07-27 | E-GEOD-51509 | biostudies-arrayexpress

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Project description:TTF-1/NKX2-1 was expressed by adenoviral vector and changes in gene expression were determined by RNA-sequencing.

2014-07-27 | GSE56356 | GEO

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Overexpression of lung developmental transcription factors TTF-1, NKX2-8 and PAX9

Project description:We investigated the clinical implications of lung developmental transcription factors (TTF-1, NKX2-8, and PAX9) which we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the three genes were determined and used to risk stratify a non-small cell lung cancer (NSCLC) clinical dataset consisting of ninety-one early stage tumors. Co-activation of the TTF-1 and NKX2-8 pathways identified a cluster of patients with poor survival, representing approximately 20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with co-activation of TTF-1 and NKX2-8 was validated in two other independent clinical datasets. Further, lung cancer cell lines showing co-activation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. Since TTF-1 and NKX2-8 lack specific inhibitors at the current time, we explored an alternative therapeutic strategy. Using signatures of signaling pathway activation, we identified deregulation of specific oncogenic pathways (Ras and Myc) in the TTF-1/NKX2-8 co-activated cohort. In vitro experiments demonstrated the ability of a Ras pathway-specific therapy to inhibit tumor cell growth in TTF-1/NKX-2 activated cells, thus, suggesting that modulation of the Ras pathway is a rational strategy to targeted therapy in high risk NSCLC patients with co-activation of specific lung developmental pathways. Keywords: Transcription factor expression analysis

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Transcription profiling of human bronchial epithelial cells overexpressing the lung developmental transcription factors TTF1, NKX2-8 and PAX9

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2014-07-27 | E-GEOD-49675 | biostudies-arrayexpress

TTF-1/NKX2-1 and ASCL1 binding regions in NCI-H209 and NKX2-1 binding regions in NCI-H441, replicate 2

Project description:Although Thyroid transcription factor-1 (TTF-1, encoded by NKX2-1 gene) is highly expressed in small cell lung carcinoma (SCLC) and lung adenocarcinoma (LADC), difference in the functional roles of TTF-1 between SCLC and LADC remains to be elucidated. The aim of this study was to clarify the differences in the TTF-1 binding regions and functional roles in SCLC and LADC. Employing chromatin immunoprecipitation-sequencing (ChIP-seq) , here we compared the genome-wide TTF-1-binding profiles and the TTF-1-mediated transcriptional programs in a SCLC and a LADC cell lines. We also investigated ASCL1 binding regions in SCLC cells.

2019-11-30 | GSE139868 | GEO

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