Ectopic expression of Neuronatin potentiates adipogenesis through enhanced phosphorylation of cAMP-response element-binding protein in 3T3-L1 cells

Suh, Young Ho; Kim, Won‐Ho; Moon, Changsuk; Hong, Yong Tae; Eun, Su-Yong; Lim, Joo Hyun; Choi, Joo Sun; Song, Jihyun; Jung, Myeong Ho

doi:10.1016/j.bbrc.2005.09.078

Cited by 57 publications

(74 citation statements)

References 26 publications

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“…Based on its structure and localization to the endoplasmic reticulum, NNAT may be involved in regulating intracellular calcium levels. Indeed, ectopic expression of NNAT stimulated 3T3-L1 adipocytes to differentiate into mature adipocytes by increasing intracellular calcium levels and enhancing cAMP-responsive element-binding protein (CREB) phosphorylation (Suh et al, 2005). NNAT was found to undergo LOI in 69% of leukemia samples in one study, although its effects on cell growth were not analysed (Kuerbitz et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer

et al. 2006

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Lung cancer is the leading cause of cancer-related deaths in the United States due, in large part, to the lack of early detection methods. Lung cancer arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as DNA methylation and histone acetylation, are reversible with currently available pharmaceuticals and are early events in lung tumorigenesis detectable by non-invasive methods. In order to better understand how epigenetic changes contribute to lung cancer, and to identify new disease biomarkers, we combined pharmacologic inhibition of DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more than 200 genes upregulated by these treatments, three of these, neuronatin, metallothionein 3 and cystatin E/M, were frequently hypermethylated and transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly, four other genes, cylindromatosis, CD9, activating transcription factor 3 and oxytocin receptor, were dominantly regulated by histone deacetylation and were also frequently downregulated in lung tumors. The majority of these genes also suppressed NSCLC growth in culture when ectopically expressed. This study therefore reveals new putative NSCLC growth regulatory genes and epigenetic disease biomarkers that may enhance early detection strategies and serve as therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer

et al. 2006

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“…In the pituitary, serial analysis of gene expression has identified NNAT as the fifth most abundant transcript after GH, pro-opiomelanocortin, PRL and an unknown transcript, and this and other studies also show that this transcript is not expressed at significant levels in most other adult tissues (Usui et al 1997, Nishida et al 2005, Suh et al 2005. In the brain, NNAT is thought to participate in maintaining segment identity and the overall structure of the nervous system (Wijnholds et al 1995).…”

Section: Introductionmentioning

confidence: 90%

Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma

Revill¹,

Dudley²,

Clayton³

et al. 2009

Endocrine-Related Cancer

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The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this report, we determined the expression pattern of NNAT in individual cell types of the normal gland and within each of the different pituitary adenoma subtypes. In addition, we determined associations between expression and CpG island methylation and used colony forming efficiency assays (CFE) to gain further insight into the tumour-suppressor function of this gene. Immunohistochemical (IHC) co-localization studies of normal pituitaries showed that each of the hormone secreting cells (GH, PRL, ACTH, FSH and TSH) expressed NNAT. However, 33 out of 47 adenomas comprising, 11 somatotrophinomas, 10 prolactinomas, 12 corticotrophinomas and 14 non-functioning tumours, irrespective of subtype failed to express either NNAT transcript or protein as determined by quantitative real-time RT-PCR and IHC respectively. In normal pituitaries and adenomas that expressed NNAT the promoter-associated CpG island showed characteristics of an imprinted gene where w50% of molecules were densely methylated. However, in the majority of adenomas that showed loss or significantly reduced expression of NNAT, relative to normal pituitaries, the gene-associated CpG island showed significantly increased methylation.

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“…The Nnat gene was originally discovered from a differential display on the developing rat brain. However, Nnat also appears to be abundantly expressed in adipose tissue, and is significantly elevated in adipose tissue of obese Zuker diabetic fatty rats, compared with control lean Zuker rats [45]. Tpm1 is known to associate with microfilaments, also a component of the cytoskeleton in preadipocytes.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Adipose Tissues in Obesity Susceptible and Resistant Rats under a High Fat Diet

Joo¹,

Yun²

2011

Cell Physiol Biochem

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Different responses to a high fat diet (HFD) can occur even within a group of animals with the same genetic background, such as obesity-prone (OP) or obesity-resistant (OR) phenotypes, on the same feeding. To explain these phenotypes, we performed an analysis of gene expression differences in brown (BAT) and white adipose tissue (WAT) of OP and OR rats. Microarray analysis of transcripts revealed that 91 and 53 genes showed significant differences in expression between the BAT and WAT gene, respectively. Surprisingly, a majority of these genes were significantly down-regulated in adipose tissues in response to HFD feeding. K-means clustering of the expression levels of these genes identified 4 distinct groupings of genes with significant expression levels. Only a limited number of genes were significantly regulated in adipose tissues in response to HFD feeding, whereas expression levels of a large number of genes differed significantly between OP and OR rat. Our observations support that distinct discrepancies exist in gene-expression regulations in adipose tissues, and that alteration likely resulted from significant differences in genes encoding metabolic enzymes. To the best of our knowledge, this study provided the first direct comparison of gene-expression changes between OP and OR rats.

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Ectopic expression of Neuronatin potentiates adipogenesis through enhanced phosphorylation of cAMP-response element-binding protein in 3T3-L1 cells

Cited by 57 publications

References 26 publications

Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer

Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer

Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma

Gene Expression Profiling of Adipose Tissues in Obesity Susceptible and Resistant Rats under a High Fat Diet

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