Involvement of GTA protein NC2beta in neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation.
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 NC2beta (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 NC2alpha (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 NC2beta mRNA had also genomic deletions at the corresponding locus.


CONCLUSIONS
Our data show that NC2beta is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2beta, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.
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. dipietro@unict.it
Cinzia
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Di Pietro
Marco
M
Ragusa
Davide
D
Barbagallo
Laura R
LR
Duro
Maria R
MR
Guglielmino
Alessandra
A
Majorana
Veronica
V
Giunta
Antonella
A
Rapisarda
Elisa
E
Tricarichi
Marco
M
Miceli
Rosario
R
Angelica
Agata
A
Grillo
Barbara
B
Banelli
Isabella
I
Defferari
Stefano
S
Forte
Alessandro
A
Laganà
Camillo
C
Bosco
Rosalba
R
Giugno
Alfredo
A
Pulvirenti
Alfredo
A
Ferro
Karl H
KH
Grzeschik
Andrea
A
Di Cataldo
Gian P
GP
Tonini
Massimo
M
Romani
Michele
M
Purrello
D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics; D035362:Transcription Factor TFIID / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C470012:TAF12 protein, human; C113945:TAF13 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; C075995:down-regulator of transcription 1