Expression of the HMGI(Y) gene products in human neuroblastic tumours correlates with differentiation status.
HMGI and HMGY are splicing variants of the HMGI(Y) gene and together with HMGI-C, belong to a family of DNA binding proteins involved in maintaining active chromatin conformation and in the regulation of gene transcription. The expression of the HMGI(Y) gene is maximal during embryonic development, declines in adult differentiated tissues and is reactivated in most transformed cells in vitro and in many human cancers in vivo. The HMGI(Y) genomic locus is frequently rearranged in mesenchymal tumours, suggesting a biological role for HMGI(Y) gene products in tumour biology. HMGIs are both target and modulators of retinoic acid activity. In fact, HMGI(Y) gene expression is differentially regulated by retinoic acid in retinoid-sensitive and -resistant neuroblastoma cells, while HMGI-C participates in conferring retinoic acid resistance in some neuroblastoma cells. In this paper we show that HMGI and HMGY isoforms are equally regulated by retinoic acid in neuroblastoma cell lines at both RNA and protein levels. More importantly our immunohistochemical analysis shows that, although HMGI(Y) is expressed in all neuroblastic tumours, consistently higher levels are observed in less differentiated neuroblastomas compared to more differentiated ganglioneuromas, indicating that HMGI(Y) expression should be evaluated as a potential diagnostic and prognostic marker in neuroblastic tumours.
Giannini
G
G
Department of Experimental Medicine and Pathology, University La Sapienza, Rome 00161, Italy.
Kim
C J
CJ
Di Marcotullio
L
L
Manfioletti
G
G
Cardinali
B
B
Cerignoli
F
F
Ristori
E
E
Zani
M
M
Frati
L
L
Screpanti
I
I
Guilino
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D018305:Ganglioneuroblastoma / Q000235:genetics / Q000378:metabolism; D005729:Ganglioneuroma / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D025741:HMGA1a Protein; D014212:Tretinoin