Research article

Histone H1x is highly expressed in human neuroendocrine cells and tumours

Julia Warneboldt¹ , Florian Haller² , Olaf Horstmann^3,5 , Bernhard C Danner⁴ , László Füzesi² , Detlef Doenecke¹ and Nicole Happel¹

¹  Institute for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany

²  Department of Gastroenteropathology, University Medicine Göttingen, Robert-Koch-Str. 40, D-37099 Göttingen, Germany

³  Department of General- and Visceral Surgery, University Medicine Göttingen, Robert-Koch-Str. 40, D-37099 Göttingen, Germany

⁴  Department of Cardiothoracic and Vascular Surgery, University Medicine Göttingen, Robert-Koch-Str. 40, D-37099 Göttingen, Germany

⁵  Sana Kliniken Düsseldorf GmbH, Gräulinger Str. 120, D-40625 Düsseldorf, Germany

author email corresponding author email

BMC Cancer 2008, 8:388doi:10.1186/1471-2407-8-388

Published:	24 December 2008

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.