A correction for this article has been published in Molecular Cancer 2008, 7:59

Research

Involvement of GTA protein NC2β in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation

Cinzia Di Pietro¹ , Marco Ragusa¹ , Davide Barbagallo¹ , Laura R Duro¹ , Maria R Guglielmino¹ , Alessandra Majorana¹ , Veronica Giunta¹ , Antonella Rapisarda¹ , Elisa Tricarichi¹ , Marco Miceli¹ , Rosario Angelica¹ , Agata Grillo² , Barbara Banelli³ , Isabella Defferari⁴ , Stefano Forte¹ , Alessandro Lagan๠, Camillo Bosco¹ , Rosalba Giugno⁵ , Alfredo Pulvirenti⁵ , Alfredo Ferro¹ , Karl H Grzeschik⁶ , Andrea Di Cataldo⁷ , Gian P Tonini⁴ , Massimo Romani³ and Michele Purrello¹

¹  Dipartimento di Scienze Biomediche, Sezione di Biologia Generale, Biologia Cellulare, Genetica Molecolare G Sichel, Unità di Biologia Genomica e dei Sistemi Complessi, Genetica, Bioinformatica, Università di Catania, 95123 Catania, Italy

²  Labogen, 95124 Catania, Italy

³  Istituto Nazionale per la Ricerca sul Cancro (IST), Sezione di Genetica dei Tumori, 16132 Genova, Italy

⁴  Istituto Nazionale per la Ricerca sul Cancro (IST), Sezione di Oncologia Traslazionale Pediatrica, 16132 Genova, Italy

⁵  Dipartimento di Matematica ed Informatica, Università di Catania, 95123 Catania, Italy

⁶  Medizinisches Zentrum für Humangenetik, Philipps Universität, 35037 Marburg, Germany

⁷  Dipartimento di Pediatria, Università di Catania, 95123 Catania, Italy

author email corresponding author email

Molecular Cancer 2008, 7:52doi:10.1186/1476-4598-7-52

Published:	6 June 2008

Abstract

Background

The General Transcription Apparatus (GTA) comprises more than one hundred proteins, including RNA Polymerases, GTFs, TAFs, Mediator, and cofactors such as heterodimeric NC2. This complexity contrasts with the simple mechanical role that these proteins are believed to perform and suggests a still uncharacterized participation to important biological functions, such as the control of cell proliferation.

Results

To verify our hypothesis, we analyzed the involvement in Neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2β (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2α (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2β mRNA had also genomic deletions at the corresponding locus.

Conclusion

Our data show that NC2β is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2β, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.