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Molecular and Cellular Biology, April 2003, p. 2991-2998, Vol. 23, No. 8
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.8.2991-2998.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype

Ina Poser,1 Michaela Golob,1 Reinhard Buettner,2 and Anja K. Bosserhoff1*

Institute of Pathology, University of Regensburg, 93053 Regensburg,1 Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany2

Received 16 August 2002/ Returned for modification 17 September 2002/ Accepted 29 January 2003

Malignant transformation of melanocytes to melanoma cells closely parallels activation of melanoma inhibitory activity (MIA) expression. We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element. We further observed that the HCR element interacts with the melanoma-associated transcription factor (MATF) and thereby confers strong promoter activation. In this study we identify the peptide sequence of MATF and show that it is identical with the transcription factor HMG1. HMG1 was upregulated in malignant melanoma cells and further activated by hypophosphorylation. Stable antisense-HMG1 expression in melanoma cells led to the reduction of MIA promoter activity and protein expression, indicating that HMG1 is a potent regulator of MIA expression. Interestingly, chromatin immunoprecipitation and electrophoretic mobility shift experiments indicated that HMG1 and the NF-{kappa}B family member p65 both interact and bind to the HCR promoter element. In summary, our study proves HMG1 and p65 to be important factors in MIA regulation and melanoma progression.

* Corresponding author. Mailing address: Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Phone: 49-941-944-6705. Fax: 49-941-944-6602. E-mail: anja.bosserhoff{at}klinik.uni-regensburg.de.

Molecular and Cellular Biology, April 2003, p. 2991-2998, Vol. 23, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.8.2991-2998.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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