Downregulation of hASH1 is associated with the retinoic acid-induced differentiation of human neuroblastoma cell lines

Background. MASH1, a transcription factor with basic helix-loop-helix domai n, has a pivotal function to promote differentiation of neural crest cells into autonomic neurons. Procedure. To investigate the functional significan ce of human MASH1 (hASH1) in the pathogenesis of neuroblastoma, which is or iginated from autonomic precursor cells, we studied hASH1 gene expression i n primary neuroblastomas and human neuroblastoma cell lines. Results. The f ollowing results were obtained: (i) hASH1 was expressed in 40 out of 61 (66 %) primary neuroblastomas, (ii) hASH1 transcripts were downregulated in sev eral cell lines prior to differentiation induced by all-trans retinoic acid (RA), (iii) a neuroblastoma cell line without expression of endogenous hAS H1 did not respond to RA at all, and (iv) the analysis of the hASH1 genomic DNA revealed two possible transcription initiation sites, which may corres pond to 3.0 kb and 3.5 kb transcripts. Conclusions. Our observations sugges t that, although hASH1 may not preserve the growth capacity of neuroblastom as, downregulation of hASH1 may be necessary to promote neuronal differenti ation of neuroblastoma. Med. Pediatr. Oncol. 36:132-134, 2001. (C) 2001 Wil ey-Liss. Inc.