Evaluation of genes identified by microarray analysis in favorable neuroblastoma

Kamei, Naosuke; Hiyama, Keiko; Yamaoka, Hiroaki; Kamimatsuse, Arata; Onitake, Yoshiyuki; Sueda, Taijiro; Hiyama, Eiso

doi:10.1007/s00383-009-2448-1

Cited by 13 publications

(11 citation statements)

References 12 publications

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“…The up-regulated expression may limit the activity of RA, which is generally thought to have an inhibitory effect on the cell cycle and promote apoptosis in some cancer cell lines (6), thereby exerting a prosurvival effect. However, despite the enhanced expression, DHRS3 was negatively correlated with metastasis in papillary thyroid carcinomas (39), associated with better prognosis in neuroblastoma (41), and found to have a methylated promoter, an indicator of gene silencing, in a subset of human malignant melanomas (42), all consistent with a potential favorable role in tumor suppression. Given the well established role of p53 in tumor suppression and the validation of DHRS3 as a bona fide p53 target gene (17), it will be worthwhile to investigate any potential cross-talk between p53, DHRS3, and retinoid signaling as they relate to inhibition or promotion of tumor initiation and progression.…”

Section: Discussionmentioning

confidence: 91%

“…DHRS3 expression was shown to be up-regulated in transformed buccal keratinocytes (38), papillary thyroid carcinomas (39,40), and neuroblastomas (41). The up-regulated expression may limit the activity of RA, which is generally thought to have an inhibitory effect on the cell cycle and promote apoptosis in some cancer cell lines (6), thereby exerting a prosurvival effect.…”

Section: Discussionmentioning

confidence: 99%

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p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation

Deisenroth

Itahana

Tollini

et al. 2011

Journal of Biological Chemistry

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The transcription factor p53 plays a critical role in maintaining homeostasis as it relates to cellular growth, proliferation, and metabolism. In an effort to identify novel p53 target genes, a microarray approach was utilized to identify DHRS3 (also known as retSDR1) as a robust candidate gene. DHRS3 is a highly conserved member of the short chain alcohol dehydrogenase/reductase superfamily with a reported role in lipid and retinoid metabolism. Here, we demonstrate that DHRS3 is an endoplasmic reticulum (ER) protein that is shuttled to the ER via an N-terminal endoplasmic reticulum targeting signal. One important function of the ER is synthesis of neutral lipids that are packaged into lipid droplets whose biogenesis occurs from ER-derived membranes. DHRS3 is enriched at focal points of lipid droplet budding where it also localizes to the phospholipid monolayer of ER-derived lipid droplets. p53 promotes lipid droplet accumulation in a manner consistent with DHRS3 enrichment in the ER. As a p53 target gene, the observations of Dhrs3 location and potential function provide novel insight into an unexpected role for p53 in lipid droplet dynamics with implications in cancer cell metabolism and obesity.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation

Deisenroth

Itahana

Tollini

et al. 2011

Journal of Biological Chemistry

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“…Each array was composed of 1,250 different probes. The genes present on the microarray are all part of the human whole genome microarray which has been extensively used in the literature (Guo et al 2006; Hiyama et al 2009; Kamei et al 2009). To perform cDNA amplification and hybridization the Codelink™ iExpress iAmplify cRNA Prep & Hyb Kit of Applied Microarrays (Tempe, AZ, USA) was used according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins

et al. 2012

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In the pharmaceutical industry, improving the early detection of drug-induced hepatotoxicity is essential as it is one of the most important reasons for attrition of candidate drugs during the later stages of drug development. The first objective of this study was to better characterize different cellular models (i.e., HepG2, HepaRG cells, and fresh primary human hepatocytes) at the gene expression level and analyze their metabolic cytochrome P450 capabilities. The cellular models were exposed to three different CYP450 inducers; beta-naphthoflavone (BNF), phenobarbital (PB), and rifampicin (RIF). HepG2 cells responded very weakly to the different inducers at the gene expression level, and this translated generally into low CYP450 activities in the induced cells compared with the control cells. On the contrary, HepaRG cells and the three human donors were inducible after exposure to BNF, PB, and RIF according to gene expression responses and CYP450 activities. Consequently, HepaRG cells could be used in screening as a substitute and/or in complement to primary hepatocytes for CYP induction studies. The second objective was to investigate the predictivity of the different cellular models to detect hepatotoxins (16 hepatotoxic and 5 nonhepatotoxic compounds). Specificity was 100% with the different cellular models tested. Cryopreserved human hepatocytes gave the highest sensitivity, ranging from 31% to 44% (depending on the donor), followed by lower sensitivity (13%) for HepaRG and HepG2 cells (6.3%). Overall, none of the models under study gave desirable sensitivities (80–100%). Consequently, a high metabolic capacity and CYP inducibility in cell lines does not necessarily correlate with a high sensitivity for the detection of hepatotoxic drugs. Further investigations are necessary to compare different cellular models and determine those that are best suited for the detection of hepatotoxic compounds.

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“…Array-chromosomal comparative genomic hybridization (CGH), which provides information regarding overall genomic instability, has been shown to add critical prognostic information to individual genetic aberrations [8,9]. The prognostic effects of mRNA gene expression profiles on neuroblastoma patient outcomes have also been reported by numerous investigators [10–19]. De Preter and co-workers [20] have built an independently prognostic 42-gene signature based on the reanalysis of gene expression studies using different microarray platforms comprising 582 patients.…”

Section: The International Neuroblastoma Risk Group (Inrg) Classificamentioning

confidence: 99%

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Zage

Louis

Cohn

2012

Pediatric Blood & Cancer

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Neuroblastoma is the most common extracranial solid tumor of childhood, and the outcomes for children with high‐risk and relapsed disease remain poor. However, new international strategies for risk stratification and for treatment based on novel tumor targets and including immunotherapy are being employed in attempts to improve the outcomes of children with neuroblastoma. A new international neuroblastoma risk classification system has been developed which is being incorporated into cooperative group clinical trials in North America, Japan, and Europe, resulting in standardized approaches for the initial evaluation and treatment stratification of neuroblastoma patients. Furthermore, novel treatment regimens are being developed based on improved understanding of neuroblastoma biology and on the recruitment of the immune system to specifically target neuroblastoma tumors. These approaches will lead to new therapeutic strategies that likely will improve the outcomes for children with neuroblastoma worldwide. Pediatr Blood Cancer 2012; 58: 1099–1105. © 2012 Wiley Periodicals, Inc.

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Evaluation of genes identified by microarray analysis in favorable neuroblastoma

Abstract: Using microarray expression profiling, we identified genes that exhibit altered gene expression in neuroblastoma tumors associated with a favorable outcome. These candidates warrant further study for use in risk assessment and/or as therapeutic targets in neuroblastoma.

Cited by 13 publications

References 12 publications

p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation

p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation

Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

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