Histone HIx is highly expressed in human neuroendocrine cells and tumours

Background: Histone HIx is a ubiquitously expressed member of the HI histone family. HI 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 HI 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 HIx in libraries from neuroendocrine tumours (NETs), we evaluated the expression of HIx in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of HIx 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 HI.0 during tumourigenesis, the analysis of this subtype was included in this study. Results: We found an increased expression of HIx but not of HI.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 HIx compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of HIx and chromogranin A in sections of pancreas and small intestine revealed that HIx is highly expressed in neuroendocrine cells of these tissues. Conclusion: We conclude that the high expression of histone HIx in NETs is probably due to the abundance of this protein in the cells from which these tumours originate.