Molecular mechanism of HMGA1 deregulation in human neuroblastoma.
Very soon after their original identification in HeLa cells in 1983, HMGA proteins appeared as interesting cancer-related molecules. Indeed, they were immediately noted as a sub-class of High Mobility Group proteins induced in fibroblast or epithelial cells transformed with sarcoma viruses. After more than 20 years, the association between HMGA protein expressions and cellular transformation has been largely confirmed and HMGA are among the most widely expressed cancer-associated proteins. Nevertheless, their functional contribution to tumour development and progression is far from being completely understood. Furthermore, although HMGA1 expression has been reported to be inducible by a number of factors and circumstances, the question of how their expression is deregulated in cancer is even less clear and somehow has been ignored from most researchers. An active AP1 site is the only characterized element of the HMGA1 human promoter, that remains a rather complicated and unexplored source of information to answer this question. Following the indication that c-Myc might bind and activate the mouse HMGA1 gene promoter, we have demonstrated that HMGA1 is a new target for MYCN in human neuroblastomas. In this report, we overview part of the current information on HMGA1 and focus our attention on the analysis of its human promoter.
Giannini
Giuseppe
G
Department of Experimental Medicine and Pathology, Department of Pediatrics, University La Sapienza, Policlinico Umberto 1, Viale Regina Elena, 324, 00161 Rome, Italy. giuseppe.giannini@uniroma1.it
Cerignoli
Fabio
F
Mellone
Massimiliano
M
Massimi
Isabella
I
Ambrosi
Cinzia
C
Rinaldi
Christian
C
Gulino
Alberto
A
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology
D025741:HMGA1a Protein