Peg3/Pw1 is an imprinted gene involved in the TNF-NFκB signal transduction pathway

Relaix, Frédéric; Wei, Xiaorong; Wu, Xiangwei; Sassoon, David

doi:10.1038/ng0398-287

Cited by 149 publications

(146 citation statements)

References 34 publications

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“…Among these were putative tumour suppressors including the p53 mediator paternally expressed gene-3 (PEG-3) (Relaix et al, 1998;Deng and Wu, 2000), wnt-inducible signalling protein-2 (WISP-2), a member of the connective tissue growth factor family (Pennica et al, 1998), and the Rho-associated transcriptional coactivator four-and-a-half LIM domains 2 (FHL2) (Muller et al, 2002). However, the recently reported putative tumour suppressor in ovarian cancer, opioid-binding protein (OPCML), did not appear to have significant loss of expression in any of the samples studied here (Sellar et al, 2003) ( Figure 2E).…”

Section: Primary Ovarian Diseasementioning

confidence: 99%

Predicting biomarkers for ovarian cancer using gene-expression microarrays

et al. 2004

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Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Here, we used oligonucleotide microarrays complementary to B12 000 genes to establish a gene-expression microarray (GEM) profile for normal ovarian tissue, as compared to stage III ovarian serous adenocarcinoma and omental metastases from the same individuals. We found that the GEM profiles of the primary and secondary tumours from the same individuals were essentially alike, reflecting the fact that these tumours had already metastasised and acquired the metastatic phenotype. We have identified a novel biomarker, mammaglobin-2 (MGB2), which is highly expressed specific to ovarian cancer. MGB2, in combination with other putative markers identified here, could have the potential for screening. Ovarian cancer is the leading cause of death from gynaecological malignancy, with an estimated 24 000 and 6800 new cases in the US and UK, respectively, during (Greenlee et al, 2001Swerdlow et al, 2001). Early-stage disease is largely asymptomatic, and most patients are diagnosed when disease has spread beyond the pelvis with an associated 5-year survival of less than 20% (Ozols, 2002). This is partly due to the lack of reliable screening strategies. While around 90% of women with advanced disease have elevated serum CA125, this marker alone is neither sufficiently sensitive nor specific for use as a screening tool (Menon and Jacobs, 2001). Despite new cytotoxic regimens, survival has remained largely unchanged over the past 20 years. Identification of new molecular signatures of early disease is a key goal of ovarian cancer research.Gene-expression microarray (GEM) profiles have previously been used to compare the expression profile of ovarian cancer with that of the normal ovary (Ono et al, 2000;Welsh et al, 2001). We extended this approach by using a more extensive set of probes (Affymetrix U95Av2), and also characterised metastatic disease in a search for molecular markers of progression. We investigated the potential specificity of a number of putative biomarkers by examining their expression in a panel of other epithelial tissues and tumours. MATERIALS AND METHODS Ovarian tissue samplesFour snap-frozen normal ovarian samples, and six pairs of primary and omental serous adenocarcinoma (Stage IIIC) from the same individuals were collected at the time of surgery at the University College Hospitals NHS Trust. The six paired samples of primary and secondary ovarian cancer were taken at the time of primary surgery prior to chemotherapeutic intervention. The normal ovarian samples were taken at the time of surgery for benign disease. H&E-stained sections were examined and verified histopathologically to be stage III serous adenocarcinomas. All samples comprised at least 70% tumour, except one omental sample which had 5% tumour content. The normal ovarian samples were verified to be free of any pathology, including benign cysts. Ovarian epithelium was macrodissected from the underlying stroma...

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Section: Primary Ovarian Diseasementioning

confidence: 99%

Predicting biomarkers for ovarian cancer using gene-expression microarrays

et al. 2004

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“…The expression vector pcDNA3-FLAG-TRAF2DN encoding the truncated form of TRAF2 cDNA without the ®rst 86 aa and (Relaix et al, 1998) was transfected by electroporation (230V, 1050 mF) into LU1205 cells as previously described . In parallel, pcDNA3-neo vector (Invitrogen, Carlsbad, CA) was transfected to generate control LU1205-neo cells.…”

Section: Stable Transfection and Selectionmentioning

confidence: 99%

“…The reporter constructs used were: 26NF-kBLuc (Zandi et al, 1997), 56Jun2tk-Luc, 56TRE-tk-Luc and vector tk-Luc (van Dam et al, 1998). The expression constructs pcDNA3-TRAF2, pcDNA3-FLAG-TRAF2DN (Relaix et al, 1998), pCMV5-FLAG-GCK and GCK (K-H) (Yuasa et al, 1998) were also used in these experiments. CAT activity was determined as previously described (Ivanov et al, 1995).…”

Section: Transient Transfection and Luciferase Assaymentioning

confidence: 99%

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

2000

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Radiation resistance is a hallmark of human melanoma, and yet mechanisms underlying this resistance are not well understood. We recently established the role of ATF2 in this process, suggesting that stress kinases, which contribute to regulation of ATF2 stability and activity, play an important role in the acquisition of such resistance. Here we demonstrate that changes in the expression and respective activities of TRAF2/GCK occur during melanoma development and regulate its sensitivity to UV-induced apoptosis. Comparing earlyand late-stage melanoma cells revealed low expression of TRAF2 and GCK in early-stage melanoma, which coincided with poor resistance to UV-induced, TNFmediated apoptosis; forced expression of GCK alone or in combination with TRAF2 e ciently increased JNK and NF-kB activities, which coincided with increased protection against apoptosis. Conversely, forced expression of the dominant negative form of TRAF2 or GCK in late-stage melanoma cells reduced NF-kB activity and decreased Fas expression, resulting in a lower degree of UV-induced, Fas-mediated cell death. Our results illustrate a mechanism in which protection from, or promotion of, UV-induced melanoma cell death depends on the nature of the apoptotic cascade (TNF or Fas) and on the availability of TRAF2/GCK, whose expression increases during melanoma progression. Oncogene (2000) 19, 933 ± 942.

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“…This suggested a deficit in the neurobiological control of lactation, and investigations demonstrated a reduced number of oxytocin-positive neurons in the hypothalamus of Peg3 mutant females (Li et al 1999). Given the central role played by oxytocin in both maternal behaviour and milk letdown, the indication is that this is the neurobiological pathway via which Peg3 is exerting an effect (Keverne 2001), an idea that sits nicely with its involvement in the tumour necrosis factor signalling pathway affecting NFkB phosphorylation, apoptosis and cell survival (Relaix et al 1998(Relaix et al , 2000.…”

Section: The Pre-weaning Period and Mother-offspring Bondingmentioning

confidence: 99%

Genomic imprinting and the social brain

Isles

Davies

Wilkinson

2006

Phil. Trans. R. Soc. B

109

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Genomic imprinting refers to the parent-of-origin-specific epigenetic marking of a number of genes. This epigenetic mark leads to a bias in expression between maternally and paternally inherited imprinted genes, that in some cases results in monoallelic expression from one parental allele. Genomic imprinting is often thought to have evolved as a consequence of the intragenomic conflict between the parental alleles that occurs whenever there is an asymmetry of relatedness. The two main examples of asymmetry of relatedness are when there is partiality of parental investment in offspring (as is the case for placental mammals, where there is also the possibility of extended postnatal care by one parent), and in social groups where there is a sex-biased dispersal. From this evolutionary starting point, it is predicted that, at the behavioural level, imprinted genes will influence what can broadly be termed bonding and social behaviour. We examine the animal and human literature for examples of imprinted genes mediating these behaviours, and divide them into two general classes. Firstly, mother-offspring interactions (suckling, attachment and maternal behaviours) that are predicted to occur when partiality in parental investment in early postnatal offspring occurs; and secondly, adult social interactions, when there is an asymmetry of relatedness in social groups. Finally, we return to the evolutionary theory and examine whether there is a pattern of behavioural functions mediated by imprinted genes emerging from the limited data, and also whether any tangible predictions can be made with regards to the direction of action of genes of maternal or paternal origin.

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Peg3/Pw1 is an imprinted gene involved in the TNF-NFκB signal transduction pathway

Cited by 149 publications

References 34 publications

Predicting biomarkers for ovarian cancer using gene-expression microarrays

Predicting biomarkers for ovarian cancer using gene-expression microarrays

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

Genomic imprinting and the social brain

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