Skip to main content
Top
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Histone H1x is highly expressed in human neuroendocrine cells and tumours

Authors: Julia Warneboldt, Florian Haller, Olaf Horstmann, Bernhard C Danner, László Füzesi, Detlef Doenecke, Nicole Happel

Published in: BMC Cancer | Issue 1/2008

Login to get access

Abstract

Background

Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation.

Methods

Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study.

Results

We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues.

Conclusion

We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate.
Appendix
Available only for authorised users
Literature
1.
go back to reference Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ: Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997, 389: 251-260. 10.1038/38444.CrossRefPubMed Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ: Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997, 389: 251-260. 10.1038/38444.CrossRefPubMed
2.
go back to reference Kornberg RD, Lorch Y: Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999, 98: 285-294. 10.1016/S0092-8674(00)81958-3.CrossRefPubMed Kornberg RD, Lorch Y: Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999, 98: 285-294. 10.1016/S0092-8674(00)81958-3.CrossRefPubMed
3.
go back to reference Ausio J: Histone variants – the structure behind the function. Brief Funct Genomic Proteomic. 2006, 5: 228-243. 10.1093/bfgp/ell020.CrossRefPubMed Ausio J: Histone variants – the structure behind the function. Brief Funct Genomic Proteomic. 2006, 5: 228-243. 10.1093/bfgp/ell020.CrossRefPubMed
4.
go back to reference Happel N, Schulze E, Doenecke D: Characterisation of human histone H1x. Biol Chem. 2005, 386: 541-551. 10.1515/BC.2005.064.CrossRefPubMed Happel N, Schulze E, Doenecke D: Characterisation of human histone H1x. Biol Chem. 2005, 386: 541-551. 10.1515/BC.2005.064.CrossRefPubMed
5.
go back to reference Stoldt S, Wenzel D, Schulze E, Doenecke D, Happel N: G1 phase-dependent nucleolar accumulation of human histone H1x. Biol Cell. 2007, 99: 541-552. 10.1042/BC20060117.CrossRefPubMed Stoldt S, Wenzel D, Schulze E, Doenecke D, Happel N: G1 phase-dependent nucleolar accumulation of human histone H1x. Biol Cell. 2007, 99: 541-552. 10.1042/BC20060117.CrossRefPubMed
6.
go back to reference Brown DT: Histone H1 and the dynamic regulation of chromatin function. Biochem Cell Biol. 2003, 81: 221-227. 10.1139/o03-049.CrossRefPubMed Brown DT: Histone H1 and the dynamic regulation of chromatin function. Biochem Cell Biol. 2003, 81: 221-227. 10.1139/o03-049.CrossRefPubMed
7.
go back to reference Alexandrow MG, Hamlin JL: Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation. J Cell Biol. 2005, 168: 875-886. 10.1083/jcb.200409055.CrossRefPubMedPubMedCentral Alexandrow MG, Hamlin JL: Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation. J Cell Biol. 2005, 168: 875-886. 10.1083/jcb.200409055.CrossRefPubMedPubMedCentral
8.
go back to reference Downs JA, Kosmidou E, Morgan A, Jackson SP: Suppression of homologous recombination by the Saccharomyces cerevisiae linker histone. Mol Cell. 2003, 11: 1685-1692. 10.1016/S1097-2765(03)00197-7.CrossRefPubMed Downs JA, Kosmidou E, Morgan A, Jackson SP: Suppression of homologous recombination by the Saccharomyces cerevisiae linker histone. Mol Cell. 2003, 11: 1685-1692. 10.1016/S1097-2765(03)00197-7.CrossRefPubMed
10.
go back to reference Santos-Reboucas CB, Pimentel MM: Implication of abnormal epigenetic patterns for human diseases. Eur J Hum Genet. 2007, 15: 10-17. 10.1038/sj.ejhg.5201727.CrossRefPubMed Santos-Reboucas CB, Pimentel MM: Implication of abnormal epigenetic patterns for human diseases. Eur J Hum Genet. 2007, 15: 10-17. 10.1038/sj.ejhg.5201727.CrossRefPubMed
11.
go back to reference Tan KB, Borun TW, Charpentier R, Cristofalo VJ, Croce CM: Normal and neoplastic human cells have different histone H1 compositions. J Biol Chem. 1982, 257: 5337-5338.PubMed Tan KB, Borun TW, Charpentier R, Cristofalo VJ, Croce CM: Normal and neoplastic human cells have different histone H1 compositions. J Biol Chem. 1982, 257: 5337-5338.PubMed
12.
go back to reference Mannironi C, Rossi V, Biondi A, Ubezio P, Giudici G, Masera G, D'Incalci M: Comparison of histone variant synthesis in human lymphocytic leukemia cells and in normal lymphocytes. Cancer Res. 1988, 48: 3670-3675.PubMed Mannironi C, Rossi V, Biondi A, Ubezio P, Giudici G, Masera G, D'Incalci M: Comparison of histone variant synthesis in human lymphocytic leukemia cells and in normal lymphocytes. Cancer Res. 1988, 48: 3670-3675.PubMed
13.
go back to reference Goodlad GA, Clark CM: H1 histone subtype distribution and DNA topoisomerase activity in skeletal muscle of tumour-bearing rats. Cancer Lett. 1995, 98: 111-114.CrossRefPubMed Goodlad GA, Clark CM: H1 histone subtype distribution and DNA topoisomerase activity in skeletal muscle of tumour-bearing rats. Cancer Lett. 1995, 98: 111-114.CrossRefPubMed
14.
go back to reference Zlatanova J, Doenecke D: Histone H1 zero: a major player in cell differentiation?. Faseb J. 1994, 8: 1260-1268.PubMed Zlatanova J, Doenecke D: Histone H1 zero: a major player in cell differentiation?. Faseb J. 1994, 8: 1260-1268.PubMed
15.
go back to reference Kostova NN, Srebreva LN, Milev AD, Bogdanova OG, Rundquist I, Lindner HH, Markov DV: Immunohistochemical demonstration of histone H1(0) in human breast carcinoma. Histochem Cell Biol. 2005, 124: 435-443. 10.1007/s00418-005-0052-6.CrossRefPubMed Kostova NN, Srebreva LN, Milev AD, Bogdanova OG, Rundquist I, Lindner HH, Markov DV: Immunohistochemical demonstration of histone H1(0) in human breast carcinoma. Histochem Cell Biol. 2005, 124: 435-443. 10.1007/s00418-005-0052-6.CrossRefPubMed
16.
go back to reference Klöppel G, Perren A, Heitz PU: The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci. 2004, 1014: 13-27. 10.1196/annals.1294.002.CrossRefPubMed Klöppel G, Perren A, Heitz PU: The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci. 2004, 1014: 13-27. 10.1196/annals.1294.002.CrossRefPubMed
17.
go back to reference Grötzinger C: Tumour biology of gastroenteropancreatic neuroendocrine tumours. Neuroendocrinology. 2004, 80 (Suppl 1): 8-11.CrossRefPubMed Grötzinger C: Tumour biology of gastroenteropancreatic neuroendocrine tumours. Neuroendocrinology. 2004, 80 (Suppl 1): 8-11.CrossRefPubMed
18.
go back to reference Ferolla P, Faggiano A, Avenia N, Milone F, Masone S, Giampaglia F, Puma F, Daddi G, Angeletti G, Lombardi G, Santeusanio F, Colao A: Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours. Clin Endocrinol (Oxf). 2007, 66: 1-6. Ferolla P, Faggiano A, Avenia N, Milone F, Masone S, Giampaglia F, Puma F, Daddi G, Angeletti G, Lombardi G, Santeusanio F, Colao A: Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours. Clin Endocrinol (Oxf). 2007, 66: 1-6.
19.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
20.
go back to reference Krizman DB, Wagner L, Lash A, Strausberg RL, Emmert-Buck MR: The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer progression. Neoplasia. 1999, 1: 101-106. 10.1038/sj.neo.7900002.CrossRefPubMedPubMedCentral Krizman DB, Wagner L, Lash A, Strausberg RL, Emmert-Buck MR: The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer progression. Neoplasia. 1999, 1: 101-106. 10.1038/sj.neo.7900002.CrossRefPubMedPubMedCentral
21.
go back to reference Meergans T, Albig W, Doenecke D: Varied expression patterns of human H1 histone genes in different cell lines. DNA Cell Biol. 1997, 16: 1041-1049.CrossRefPubMed Meergans T, Albig W, Doenecke D: Varied expression patterns of human H1 histone genes in different cell lines. DNA Cell Biol. 1997, 16: 1041-1049.CrossRefPubMed
22.
go back to reference Parseghian MH, Hamkalo BA: A compendium of the histone H1 family of somatic subtypes: an elusive cast of characters and their characteristics. Biochem Cell Biol. 2001, 79: 289-304. 10.1139/bcb-79-3-289.CrossRefPubMed Parseghian MH, Hamkalo BA: A compendium of the histone H1 family of somatic subtypes: an elusive cast of characters and their characteristics. Biochem Cell Biol. 2001, 79: 289-304. 10.1139/bcb-79-3-289.CrossRefPubMed
23.
go back to reference Rousseau D: Uncoordinated regulation of histone H1(0)synthesis and H1(0) mRNA level. Biochem Mol Biol Int. 1996, 38: 1023-1032.PubMed Rousseau D: Uncoordinated regulation of histone H1(0)synthesis and H1(0) mRNA level. Biochem Mol Biol Int. 1996, 38: 1023-1032.PubMed
24.
go back to reference Winkler H, Fischer-Colbrie R: The chromogranins A and B: the first 25 years and future perspectives. Neuroscience. 1992, 49: 497-528. 10.1016/0306-4522(92)90222-N.CrossRefPubMed Winkler H, Fischer-Colbrie R: The chromogranins A and B: the first 25 years and future perspectives. Neuroscience. 1992, 49: 497-528. 10.1016/0306-4522(92)90222-N.CrossRefPubMed
25.
go back to reference Lamberts SW, Hofland LJ, Nobels FR: Neuroendocrine tumor markers. Front Neuroendocrinol. 2001, 22: 309-339. 10.1006/frne.2001.0218.CrossRefPubMed Lamberts SW, Hofland LJ, Nobels FR: Neuroendocrine tumor markers. Front Neuroendocrinol. 2001, 22: 309-339. 10.1006/frne.2001.0218.CrossRefPubMed
26.
go back to reference Taupenot L, Harper KL, O'Connor DT: The chromogranin-secretogranin family. N Engl J Med. 2003, 348: 1134-1149. 10.1056/NEJMra021405.CrossRefPubMed Taupenot L, Harper KL, O'Connor DT: The chromogranin-secretogranin family. N Engl J Med. 2003, 348: 1134-1149. 10.1056/NEJMra021405.CrossRefPubMed
27.
go back to reference Mauderly JL, Bice DE, Cheng YS, Gillett NA, Henderson RF, Pickrell JA, Wolff RK: Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust. Res Rep Health Eff Inst. 1989, 1-47. 30 Mauderly JL, Bice DE, Cheng YS, Gillett NA, Henderson RF, Pickrell JA, Wolff RK: Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust. Res Rep Health Eff Inst. 1989, 1-47. 30
28.
go back to reference Deyl Z, Macek K, Adam M, Vancikova O: Studies on the chemical nature of elastin fluorescence. Biochim Biophys Acta. 1980, 625: 248-254.CrossRefPubMed Deyl Z, Macek K, Adam M, Vancikova O: Studies on the chemical nature of elastin fluorescence. Biochim Biophys Acta. 1980, 625: 248-254.CrossRefPubMed
Metadata
Title
Histone H1x is highly expressed in human neuroendocrine cells and tumours
Authors
Julia Warneboldt
Florian Haller
Olaf Horstmann
Bernhard C Danner
László Füzesi
Detlef Doenecke
Nicole Happel
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-388

Other articles of this Issue 1/2008

BMC Cancer 1/2008 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine