Regular Article

British Journal of Cancer (2000) 83, 1503–1509. doi:10.1054/bjoc.2000.1494 www.bjcancer.com
Published online 14 November 2000

Expression of the HMGI(Y) gene products in human neuroblastic tumours correlates with differentiation status

G Giannini1, C J Kim2, L Di Marcotullio1, G Manfioletti3, B Cardinali4, F Cerignoli5, E Ristori1, M Zani1, L Frati1,6, I Screpanti1 and A Gulino1,6

  1. 1Department of Experimental Medicine and Pathology, University La Sapienza, Rome, 00161, Italy
  2. 2Department of Pathology, Seoul National University College of Medicine, Korea
  3. 3Department of Biochemistry, Biophysics and Chemistry of the Macromolecules, University of Trieste, Italy
  4. 4Istituto di Biologia Cellulare, CNR, Rome, Italy
  5. 5Department of Experimental Medicine, University of L'Aquila, L'Aquila, 67100, Italy
  6. 6IMN, Neuromed Institute, Pozzili, Italy

Received 4 April 2000; Revised 19 July 2000; Accepted 14 August 2000.

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Abstract

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. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords:

HMGI, neuroblastic tumours, retinoic acid

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