Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of NCI-H292 cells after treatment of TFAP2C-specific siRNA

ABSTRACT: Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus, new molecular targets need to be identified to improve treatment efficacy. Enhanced TFAP2C expression was found in lung cancer patient tissues and lung cancer cell lines, and its overexpression promoted cell proliferation and cell cycle progression. We conducted microarrays to find the possible downstream effectors regulated by TFAP2C which could play key roles in lung tumorigenesis. Two total RNA samples, extracted from NCI-H292 cells treated with or without TFAP2C siRNA, were analyzed by Affymetrix microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: BuHyun Youn

PROVIDER: E-GEOD-79228 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. Transcription factor TFAP2C plays a critical role in the regulation of both estrogen receptor-alpha (ERM-NM-1) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines representing different clinical phenotypes. Comparing the genomic binding sites for TFAP2C in the various cell lines, we identified that glutathione peroxidase (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene. Knock-down of TFAP2C, but not the related factor TFAP2A, resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity correlated with endogenous GPX1 expression, and overexpression of exogenous GPX1 induced GPX activity and significantly increased resistance to tert-butyl hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where GPX1 promoter methylation was associated with gene silencing, treatment with 5-aza-dC (an inhibitor of DNA methylation) resulted in activation of GPX1 RNA and protein expression. Methylation of the GPX1 promoter was identified in approximately 20% of primary breast cancers and a highly significant correlation between TFAP2C and GPX1 expression was confirmed when considering only those tumors with an unmethylated promoter, whereas the related factor, TFAP2A, failed to demonstrate a correlation. The results demonstrate that TFAP2C regulates the expression of GPX1, which influences the redox state and sensitivity to oxidative stress induced by peroxides. Given the established role of GPX1 in breast cancer, the results provide an important mechanism for TFAP2C to further influence oncogenesis and progression of breast carcinoma cells. 4 ChIP-Seq data for TFAP2C in human breast carcinoma cell lines MCF-7, BT-474, MDA-MB-453 and SKBR-3.

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Gene expression profiling of NCI-H292 cells after treatment of TFAP2C-specific siRNA

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