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 H MGI-C, belong to a family of DNA binding proteins involved in maintaining a ctive chromatin conformation and in the regulation of gene transcription. T he expression of the HMGI(Y) gene is maximal during embryonic development, declines in adult differentiated tissues and is reactivated in most transfo rmed cells in vitro and in many human cancers in vivo. The HMGI(Y) genomic locus is frequently rearranged in mesenchymal tumours, suggesting a biologi cal 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 -re sistant neuroblastoma cells, while HMGI-C participates in conferring retino ic acid resistance in some neuroblastoma cells. In this paper we show that HMGI and HMGY isoforms are equally regulated by retinoic acid in neuroblast oma cell lines at both RNA and protein levels. More importantly our immunoh istochemical analysis shows that, although HMGI(Y) is expressed in all neur oblastic tumours, consistently higher levels are observed in less different iated neuroblastomas compared to more differentiated ganglioneuromas, indic ating that HMGI(Y) expression should be evaluated as a potential diagnostic and prognostic marker in neuroblastic tumours, (C) 2000 Cancer Research Ca mpaign http://www.bjcancer.com.