Inactivation of DNA–Dependent Protein Kinase Promotes Heat–Induced Apoptosis Independently of Heat–Shock Protein Induction in Human Cancer Cell Lines

Okazawa, Seisuke; Furusawa, Yukihiro; Kariya, Ayako; Hassan, Mona M.; Arai, Mie; Hayashi, Ryuji; Tabuchi, Yoshiaki; Kondo, Takashi; Tobe, Kazuyuki

doi:10.1371/journal.pone.0058325

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…In the present study, GADD45B demonstrated increased mRNA levels in the EGR1-overexpressing H1299 cells. Several anti-apoptotic proteins, such as SON28, PRKDC29, and TOP130, were also downregulated in the EGR1-overexpressing cells, and several apoptotic proteins, including KRT1831, NR4A132, and TGM233, were upregulated in the same group of cells.…”

Section: Discussionmentioning

confidence: 88%

EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression

Zhang

Chen

Wang

et al. 2014

Sci Rep

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Early growth response 1 (EGR1) is a multifunctional transcription factor; Positive and negative functions of EGR1 in various tumors rely on the integrated functions of various genes it regulates. In this study, we observed the role of EGR1 in non-small-cell lung carcinoma (NSCLC) and identified genes that influence cell fate and tumor development. Various assays showed that EGR1 arrested cell mobility, inhibited migration, and induced apoptosis. Microarray analysis revealed that 100 genes, including CDKN1C, CDC27 and PRKDC, changed their mRNA expressions with the increase of EGR1 and contributed to intervention of tumor progression. Bioinformatics analysis and promoter analysis indicated that an EGR1 binding site was situated in the promoter of KRT18 (also named CK18) and KRT18 could assist in inhibition of NSCLC development. The expression level of EGR1 and KRT18 in NSCLC clinical cases was investigated by immunohistochemistry, in which the protein expression of KRT18 was found to be significantly associated with EGR1 and lymph node metastasis. The results collectively confirm that EGR1 functions as a tumor suppressor in NSCLC. This study is the first to report KRT18 expression is directly regulated by EGR1, and contributes to decrease malignancy of NSCLC.

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Section: Discussionmentioning

confidence: 88%

EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression

Zhang

Chen

Wang

et al. 2014

Sci Rep

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“…The second most frequently amplified gene (5/10 tumors) encodes the nuclear receptor NR1D1, a survival factor in a subset of breast cancers. Its driver effect might rely on its antiapoptotic activity [ 23 ] or on its known upregulation of genes involved in an abnormal aerobic glycolysis typical of cancer [ 24 ]. MMAB , found amplified in 4 out of 10 tumors, encodes the enzyme catalyzing the final step for conversion of vitamin B(12) into adenosylcobalamin.…”

Section: Resultsmentioning

confidence: 99%

Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes

et al. 2015

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BackgroundOvarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression.MethodsWe have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes.ResultsOur results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related.ConclusionsOur combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1283-0) contains supplementary material, which is available to authorized users.

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“…Earlier studies in rodent cells exposed to heat stress indicated that cell growth was promoted by the activity of DNA-dependent protein kinase (DNA-PK) (Nueda et al 1999). The absence of a functioning DNA-PK is known to be associated with down-regulation of heat shock protein 70 (HSP70) (Okazawa et al 2013). This gene has also been identified as one of the functional candidates for mastitis resistance in cattle (Schwerin et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Linkage disequilibrium and genomic scan to detect selective loci in cattle populations adapted to different ecological conditions in Ethiopia

Edea

Dadi

Kim

et al. 2014

J Animal Breeding Genetics

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Despite the wide range of observed phenotypic diversities and adaptation to different ecological conditions, little has been studied regarding the genetics of adaptation in the genome of indigenous cattle breeds of developing countries. Here, we investigated the linkage disequilibrium (LD) and identified the subset of outlier loci that are highly differentiated among cattle populations adapted to different ecological conditions in Ethiopia. Specifically, we genotyped 47 unrelated animals sampled from high- versus low-altitude environments using a Bovine 50K SNP BeadChip. Linkage disequilibrium was assessed using both D' and r(2) between adjacent SNPs. We calculated FST and heterozygosity at different significance levels as measures of genetic differentiation for each locus between high- and low-altitude populations following the hierarchical island model approach. We identified 816 loci (p < 0.01) showing selection signals and are associated with genes that might have roles in local adaptation. Some of them are associated with candidate genes that are involved in metabolism (ATP2A3, CA2, MYO18B, SIK3, INPP4A, and IREB2), hypoxia response (BDNF, TFRC, and PML) and heat stress (PRKDC, CDK1, and TFDC). Average r(2) and D' values were 0.14 ± 0.21 and 0.57 ± 0.34, respectively, for a minor allele frequency (MAF) ≥ 0.05 and were found to increase with increasing MAF value. The outlier loci identified in the studied Ethiopian cattle populations indicate the presence of genetic variation produced/shaped by adaptation to different environmental conditions and provide a basis for further validation and functional analysis using a reasonable sample size and high-density markers.

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Inactivation of DNA–Dependent Protein Kinase Promotes Heat–Induced Apoptosis Independently of Heat–Shock Protein Induction in Human Cancer Cell Lines

Cited by 15 publications

References 49 publications

EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression

EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression

Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes

Linkage disequilibrium and genomic scan to detect selective loci in cattle populations adapted to different ecological conditions in Ethiopia

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