Mapping, Characterization, and Expression Analysis of the SM-20 Human Homologue, C1orf12, and Identification of a Novel Related Gene, SCAND2

Dupuy, Denis; Aubert, Incarnation; Duperat, Véronique Guyonnet; Petit, Joëlle; Taine, Laurence; Stef, Marianne; Bloch, Bertrand; Arveiler, Benoı̂t

doi:10.1006/geno.2000.6343

Cited by 35 publications

(23 citation statements)

References 17 publications

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“…However, a putative bipartite nuclear localization signal (RRDNASGDAAKGKVKAK) in the NH 2 terminus was identified and has also been described in earlier studies (35). This prompted us to further investigate the subcellular distribution of PHD2.…”

Section: Resultsmentioning

confidence: 99%

Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.

Jokilehto

Rantanen²,

Luukkaa³

et al. 2006

Clinical Cancer Research

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Purpose: Hypoxia in tumors is associated with poor prognosis and resistance to treatment.The outcome of hypoxia is largely regulated by the hypoxia-inducible factors (HIF-1a and HIF-2a). HIFs in turn are negatively regulated by a family of prolyl hydroxylases (PHD1-3). The PHD2 isoform is the main down-regulator of HIFs in normoxia and mild hypoxia. This study was designed to analyze the correlation of the expression and subcellular localization of PHD2 with the pathologic features of human carcinomas and HIF-1a expression. Experimental Design: The expression of PHD2 was studied from paraffin-embedded normal tissue (n = 21) and head and neck squamous cell carcinoma (HNSCC; n = 44) by immunohistochemistry. Further studies included PHD2 mRNA detection and HIF-1a immunohistochemistry from HNSCC specimens as well as PHD2 immunocytochemistry from HNSCC-derived cell lines. Results: In noncancerous tissue, PHD2 is robustly expressed by endothelial cells. In epithelium, the basal proliferating layer also shows strong expression, whereas the more differentiated epithelium shows little or no PHD2 expression. In HNSCC, PHD2 shows strongly elevated expression both at the mRNA and protein level. Moreover, PHD2 expression increases in less differentiated phenotypes and partially relocalizes from the cytoplasm into the nucleus. Endogenously high nuclear PHD2 is seen in a subset of HNSCC-derived cell lines. Finally, although most of the tumor regions with high PHD2 expression show down-regulated HIF-1a, regions with simultaneous HIF-1a and PHD2 expression could be detected. Conclusions: Our results show that increased levels and nuclear translocation of the cellular oxygen sensor, PHD2, are associated with less differentiated and strongly proliferating tumors. Furthermore, they imply that even the elevated PHD2 levels are not sufficient to down-regulate HIF-1a in some tumors.

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Section: Resultsmentioning

confidence: 99%

Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.

Jokilehto

Rantanen²,

Luukkaa³

et al. 2006

Clinical Cancer Research

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“…EIT-6 appears to encode a protein with evolutionarily conserved function: there is a C. elegans EIT-6 homologue ( Figure 3a,b) that was identi®ed as an egg laying defective mutant (egl-9) (Trent et al, 1983), and several additional SM-20/EIT-6 homologues were identi®ed from various other species including several types of bacteria (Figure 3b). Surprisingly immunohistochemical analysis of the rat SM-20 gene demonstrated cytoplasmic staining, while the human SM-20 orthologue, another related human gene (SCAND2), and EIT-6 all contain putative nuclear localization signals (Dupuy et al, 2000;Wax et al, 1994). However, most of the homology between EIT-6 and SM-20 resides in the C-terminal region, while the N-terminal domain (containing the nuclear localization sequence) are divergent.…”

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confidence: 99%

Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression)

2002

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The breast cancer promoting e ects of estrogen and the chemopreventive e ects of tamoxifen are thought to be mediated by the estrogen receptor, a ligand-dependent transcription factor. Therefore, comprehensive analysis of gene expression pro®les following estrogen or tamoxifen treatment may help us better understand the role estrogen plays in tumorigenesis. We utilized SAGE (Serial Analysis of Gene Expression) technology to identify genes regulated by estrogen and tamoxifen in the ZR75-1 estrogen dependent breast cancer cell line. In this manner we have identi®ed several genes that were regulated by estrogen or tamoxifen. Here we report the identi®cation and initial characterization of EIT-6 (Estrogen Induced Tag-6), a novel nuclear protein and a new member of the evolutionarily conserved SM-20 family of growth regulatory immediate-early genes. EIT-6 appears to be a direct transcriptional target of the estrogen receptor and constitutive expression of EIT-6 promotes colony growth in human breast cancer cells. These data indicate that EIT-6 may play a role in estrogen induced cell growth.

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“…In humans, recently another gene, termed C1orf12 with homology to rat SM-20 (161/426 amino acids or 38% identical) has been described. 31 9D7 shows 61% (148/239) identity with C1orf12 and 95% identity with rat-SM20 suggesting that it is the actual human SM-20 homolog. The existence of 9D7-related human genes may also explain the additional weak bands in Northern blots of some tissues (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular RGD-motifs have been implicated in the regulation of caspases 26 and recently, caspasedependent involvement of rat SM-20 in apoptosis was demonstrated. 27 Using tBLAST, putative homologues in Rattus norvegicus (SM20: 227/239, 95% identity, accession number U06713), 28 -30 Homo sapiens (C1orf12: 148/239, 61% identity, AAG33965.1) 31 Caenorhabditis elegans (EGL-9: 95/218, 43% identity, AAD56365.1) 32,33 and Drosophila melanogaster (CG1114 gene product: 41/69, 59% identity, AAF52050.1) 34 could be identified. The function of neither of these proteins is fully understood.…”

Section: Full-size Cloning and Genomic Organization Of 9d7mentioning

confidence: 99%

Identification and characterization of 9D7, a novel human protein overexpressed in renal cell carcinoma

Klade

Dohnal

Fürst

et al. 2001

Intl Journal of Cancer

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With the objective of discovering novel tumor-associated antigens of the cancer/testis type, we compared the transcriptional profiles of renal cell carcinoma (RCC) and nontumorous kidney and further screened for genes expressed in RCC and testis, but not other normal tissues. In a first step, a representational difference analysis library consisting of approximately 1,900 RCC cDNA clones was generated. Clones were then spotted onto filters and hybridized with cDNA probes derived from a testis-specific cDNA library, a pool of RCCs and a pool of 10 healthy normal tissues, respectively. Based on strong hybridization signals with both RCC and testis, but not normal tissue probes, 185 clones were sequenced and annotated. Key words: representational difference analysis; transcriptional profiling; renal cell carcinoma; tumor-associated antigen; immunohistochemistryThe discovery of the MAGE family of proteins, based on their recognition by cytotoxic T-lymphocytes (CTL), finally settled a long-standing dispute on the existence of cancer-specific human T cell antigens. 1-7 MAGE genes are expressed in a variety of tumor types, but among normal tissues only in male germ line cells, which, however, lack MHC class I expression and hence the antigenic structures. 8 Subsequently, a number of other genes with similar expression characteristics, usually designated as cancer/ testis (C/T) antigens, were identified. These discoveries were not exclusively based on reactivity with CTLs, but also, as in the case of NY-ESO-1, on reactivity with autologous antibodies, 9,10 or on the comparison of transcript profiles of tumors and normal tissues by representational difference analysis (RDA). 11,12 Examples of antigens identified by the latter approach include the C/T antigens MAGE-1C 13 and LAGE-1. 14 Due to their broad expression in different tumor types, their tumor specificity and their ability to induce both CTL and antibody responses, C/T antigens are considered promising targets for cancer vaccines. Renal cell carcinomas (RCC), however, do not express any of the known C/T antigens at reasonable frequency. RCC seems to be an immunogenic tumor. A number of CTL clones with the capability of lysing both autologous and allogenic RCC cell lines could be raised but the corresponding antigens have not been identified yet. 15 One exception is antigen RU2AS, which is frequently expressed in RCC, but also in normal kidney, testes, bladder and liver. 16 We have set out to systematically search for new C/T antigens of RCC on the basis of their tumor-specific transcriptional profile. To this end we performed RDA between RCC and non-tumorous kidney tissue and selected for candidate antigens on the basis of hybridization with a testis-specific cDNA library. This approach led to the identification of 9D7, a novel human gene overexpressed in RCC. MATERIAL AND METHODS Tissue samples and RNA preparationTumors of the kidney and non-tumorous kidney tissue were obtained from patients who underwent radical nephrectomy. Tumor typing was done according to ...

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Mapping, Characterization, and Expression Analysis of the SM-20 Human Homologue, C1orf12, and Identification of a Novel Related Gene, SCAND2

Cited by 35 publications

References 17 publications

Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.

Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.

Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression)

Identification and characterization of 9D7, a novel human protein overexpressed in renal cell carcinoma

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