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Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Enhancer of the rudimentary gene homologue (ERH) expression pattern in sporadic human breast cancer and normal breast tissue

Authors: Menelaos Zafrakas, Inge Losen, Ruth Knüchel, Edgar Dahl

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

The human gene ERH (Enhancer of the Rudimentary gene Homologue) has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1) via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule.

Methods

The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN) on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH).

Results

Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test); the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1). These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue.

Conclusion

ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian cancer, ERH overexpression may be implicated in the initiation and/or progression of certain human malignancies. Further studies on large breast cancer tissue cohorts should determine whether ERH could function as a prognostic factor or even a drug target in the treatment of human breast cancer.
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Literature
1.
go back to reference Isomura M, Okui K, Fujiwara T, Shin S, Nakamura Y: Cloning and mapping of a novel human cDNA homologous to DROER, the enhancer of the Drosophila melanogaster rudimentary gene. Genomics. 1996, 32: 125-127. 10.1006/geno.1996.0086.CrossRefPubMed Isomura M, Okui K, Fujiwara T, Shin S, Nakamura Y: Cloning and mapping of a novel human cDNA homologous to DROER, the enhancer of the Drosophila melanogaster rudimentary gene. Genomics. 1996, 32: 125-127. 10.1006/geno.1996.0086.CrossRefPubMed
2.
go back to reference Jin T, Howard A, Golemis EA, Wang Y, Zhang YZ: Overexpression, purification, crystallization, and preliminary X-ray diffraction studies of the human transcription repressor ERH. Acta Cryst. 2005, F61: 531-533. Jin T, Howard A, Golemis EA, Wang Y, Zhang YZ: Overexpression, purification, crystallization, and preliminary X-ray diffraction studies of the human transcription repressor ERH. Acta Cryst. 2005, F61: 531-533.
3.
go back to reference Gelsthorpe M, Pulumati M, McCallum C, Dang-Vu K, Tsubota SI: The putative cell cycle gene, enhancer of rudimentary, encodes a highly conserved protein found in plants and animals. Gene. 1997, 186: 189-195. 10.1016/S0378-1119(96)00701-9.CrossRefPubMed Gelsthorpe M, Pulumati M, McCallum C, Dang-Vu K, Tsubota SI: The putative cell cycle gene, enhancer of rudimentary, encodes a highly conserved protein found in plants and animals. Gene. 1997, 186: 189-195. 10.1016/S0378-1119(96)00701-9.CrossRefPubMed
4.
go back to reference Pogge von Strandmann E, Senkel S, Ryffel GU: ERH (enhancer of rudimentary homologue), a conserved factor identical between frog and human, is a transcriptional repressor. Biol Chem. 2001, 382: 1379-1385. 10.1515/BC.2001.170.PubMed Pogge von Strandmann E, Senkel S, Ryffel GU: ERH (enhancer of rudimentary homologue), a conserved factor identical between frog and human, is a transcriptional repressor. Biol Chem. 2001, 382: 1379-1385. 10.1515/BC.2001.170.PubMed
5.
go back to reference Wojcik E, Murphy AM, Fares H, Dang-Vu K, Tsubota SI: Enhancer of rudimentaryp1, e(r)p1, a highly conserved enhancer of the rudimentary gene. Genetics. 1994, 138: 1163-1170.PubMedPubMedCentral Wojcik E, Murphy AM, Fares H, Dang-Vu K, Tsubota SI: Enhancer of rudimentaryp1, e(r)p1, a highly conserved enhancer of the rudimentary gene. Genetics. 1994, 138: 1163-1170.PubMedPubMedCentral
6.
go back to reference Schmitt AO, Specht T, Beckmann G, Dahl E, Pilarsky CP, Hinzmann B, Rosenthal A: Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues. Nucl Acids Res. 1999, 27: 4251-4260. 10.1093/nar/27.21.4251.CrossRefPubMedPubMedCentral Schmitt AO, Specht T, Beckmann G, Dahl E, Pilarsky CP, Hinzmann B, Rosenthal A: Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues. Nucl Acids Res. 1999, 27: 4251-4260. 10.1093/nar/27.21.4251.CrossRefPubMedPubMedCentral
7.
go back to reference Dahl E, Sadr-Nabavi A, Klopocki E, Betz B, Grube S, Kreutzfeld R, Himmelfarb M, An HX, Gelling S, Klaman I, Hinzmann B, Kristiansen G, Grützmann R, Kuner R, Petschke B, Rhiem K, Wiechen K, Sers C, Wiestler O, Schneider A, Höfler H, Nährig J, Dietel M, Schäfer R, Rosenthal A, Schmutzler R, Dürst M, Meindl A, Niederacher D: Systematic identification and molecular characterization of genes differentially expressed in breast and ovarian cancer. J Pathol. 2005, 205: 21-28. 10.1002/path.1687.CrossRefPubMed Dahl E, Sadr-Nabavi A, Klopocki E, Betz B, Grube S, Kreutzfeld R, Himmelfarb M, An HX, Gelling S, Klaman I, Hinzmann B, Kristiansen G, Grützmann R, Kuner R, Petschke B, Rhiem K, Wiechen K, Sers C, Wiestler O, Schneider A, Höfler H, Nährig J, Dietel M, Schäfer R, Rosenthal A, Schmutzler R, Dürst M, Meindl A, Niederacher D: Systematic identification and molecular characterization of genes differentially expressed in breast and ovarian cancer. J Pathol. 2005, 205: 21-28. 10.1002/path.1687.CrossRefPubMed
8.
go back to reference Klopocki E, Kristiansen G, Wild PJ, Klaman I, Castanos-Velez E, Singer G, Stohr R, Simon R, Sauter G, Leibiger H, Essers L, Weber B, Hermann K, Rosenthal A, Hartmann A, Dahl E: Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumours. Int J Oncol. 2004, 25: 641-649.PubMed Klopocki E, Kristiansen G, Wild PJ, Klaman I, Castanos-Velez E, Singer G, Stohr R, Simon R, Sauter G, Leibiger H, Essers L, Weber B, Hermann K, Rosenthal A, Hartmann A, Dahl E: Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumours. Int J Oncol. 2004, 25: 641-649.PubMed
9.
go back to reference Zafrakas M, Chorovicer M, Klaman I, Kristiansen G, Wild PJ, Heindrichs U, Knüchel-Clarke R, Dahl E: Systematic characterization of GABRP expression in sporadic breast cancer and normal breast tissue. Int J Cancer. 2006, 118: 1453-1459. 10.1002/ijc.21517.CrossRefPubMed Zafrakas M, Chorovicer M, Klaman I, Kristiansen G, Wild PJ, Heindrichs U, Knüchel-Clarke R, Dahl E: Systematic characterization of GABRP expression in sporadic breast cancer and normal breast tissue. Int J Cancer. 2006, 118: 1453-1459. 10.1002/ijc.21517.CrossRefPubMed
10.
go back to reference Veeck J, Chorovicer M, Naami A, Breuer E, Zafrakas M, Bektas M, Dürst M, Kristiansen G, Wild PJ, Hartmann A, Knuechel R, Dahl E: The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation. Oncogene. 2008, 27: 865-876. 10.1038/sj.onc.1210669.CrossRefPubMed Veeck J, Chorovicer M, Naami A, Breuer E, Zafrakas M, Bektas M, Dürst M, Kristiansen G, Wild PJ, Hartmann A, Knuechel R, Dahl E: The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation. Oncogene. 2008, 27: 865-876. 10.1038/sj.onc.1210669.CrossRefPubMed
11.
go back to reference Koensgen D, Mustea A, Klaman I, Sun PM, Zafrakas M, Lichtenegger W, Denkert C, Dahl E, Sehouli J: Expression analysis and RNA-localization of PAI-RBP1 (SERBP1) in epithelial ovarian cancer: association with tumour progression. Gynecol Oncol. 2007, 107: 266-273. 10.1016/j.ygyno.2007.06.023.CrossRefPubMed Koensgen D, Mustea A, Klaman I, Sun PM, Zafrakas M, Lichtenegger W, Denkert C, Dahl E, Sehouli J: Expression analysis and RNA-localization of PAI-RBP1 (SERBP1) in epithelial ovarian cancer: association with tumour progression. Gynecol Oncol. 2007, 107: 266-273. 10.1016/j.ygyno.2007.06.023.CrossRefPubMed
12.
go back to reference Wan C, Tempel W, Liu ZJ, Wang BC, Rose RB: Structure of the conserved transcriptional repressor enhancer of rudimentary homolog. Biochemistry. 2005, 44: 5017-5023. 10.1021/bi047785w.CrossRefPubMed Wan C, Tempel W, Liu ZJ, Wang BC, Rose RB: Structure of the conserved transcriptional repressor enhancer of rudimentary homolog. Biochemistry. 2005, 44: 5017-5023. 10.1021/bi047785w.CrossRefPubMed
13.
go back to reference Smyk A, Szuminska M, Uniewicz KA, Graves LM, Kozlowski P: Human enhancer of rudimentary is a molecular partner of PDIP46/SKAR, a protein interacting with DNA polymerase delta and S6K1 and regulating cell growth. FEBS J. 2006, 273: 4728-4741. 10.1111/j.1742-4658.2006.05477.x.CrossRefPubMed Smyk A, Szuminska M, Uniewicz KA, Graves LM, Kozlowski P: Human enhancer of rudimentary is a molecular partner of PDIP46/SKAR, a protein interacting with DNA polymerase delta and S6K1 and regulating cell growth. FEBS J. 2006, 273: 4728-4741. 10.1111/j.1742-4658.2006.05477.x.CrossRefPubMed
14.
go back to reference Lukasik A, Uniewicz KA, Kulis M, Kozlowski P: Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog. FEBS J. 2008, 275: 332-340.CrossRefPubMed Lukasik A, Uniewicz KA, Kulis M, Kozlowski P: Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog. FEBS J. 2008, 275: 332-340.CrossRefPubMed
15.
go back to reference Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB: Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003, 11: 1055-1066. 10.1016/S1097-2765(03)00101-1.CrossRefPubMed Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB: Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003, 11: 1055-1066. 10.1016/S1097-2765(03)00101-1.CrossRefPubMed
16.
go back to reference Amente S, Napolitano G, Licciardo P, Monti M, Pucci P, Lania L, Majello B: Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation. FEBS Lett. 2005, 579: 683-689. 10.1016/j.febslet.2004.12.045.CrossRefPubMed Amente S, Napolitano G, Licciardo P, Monti M, Pucci P, Lania L, Majello B: Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation. FEBS Lett. 2005, 579: 683-689. 10.1016/j.febslet.2004.12.045.CrossRefPubMed
Metadata
Title
Enhancer of the rudimentary gene homologue (ERH) expression pattern in sporadic human breast cancer and normal breast tissue
Authors
Menelaos Zafrakas
Inge Losen
Ruth Knüchel
Edgar Dahl
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-145

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