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

2003 ◽  
Vol 23 (8) ◽  
pp. 2991-2998 ◽  
Author(s):  
Ina Poser ◽  
Michaela Golob ◽  
Reinhard Buettner ◽  
Anja K. Bosserhoff

ABSTRACT 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-κB 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.

2003 ◽  
Vol 83 (11) ◽  
pp. 1583-1594 ◽  
Author(s):  
Anja-Katrin Bosserhoff ◽  
Raphael Stoll ◽  
Jonathan P Sleeman ◽  
Frauke Bataille ◽  
Reinhard Buettner ◽  
...  

2015 ◽  
Vol 13 (Suppl 1) ◽  
pp. P11
Author(s):  
Angela Sandru ◽  
Silviu Voinea ◽  
Eugenia Panaitescu ◽  
Madalina Bolovan ◽  
Adina Stanciu ◽  
...  

2004 ◽  
Vol 11 (6) ◽  
pp. 408-418 ◽  
Author(s):  
Frank Schoensiegel ◽  
Annette Paschen ◽  
Stephanie Sieger ◽  
Helmut Eskerski ◽  
Walter Mier ◽  
...  

2015 ◽  
Vol 13 (Suppl 1) ◽  
pp. P10
Author(s):  
Angela Sandru ◽  
Silviu Voinea ◽  
Eugenia Panaitescu ◽  
Madalina Bolovan ◽  
Adina Stanciu ◽  
...  

2000 ◽  
Vol 83 (9) ◽  
pp. 1216-1222 ◽  
Author(s):  
M Guba ◽  
A-K Bosserhoff ◽  
M Steinbauer ◽  
C Abels ◽  
M Anthuber ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Angela Sandru ◽  
Eugenia Panaitescu ◽  
Silviu Voinea ◽  
Madalina Bolovan ◽  
Adina Stanciu ◽  
...  

Background. Cutaneous malignant melanoma (CMM) is a heterogeneous disease, acknowledged for its lack of predictability regarding clinical evolution. In order to appreciate a patient’s individual prognosis, an attempt is made to find new tumor markers that parallel the disease progression.Objective. To identify if melanoma inhibitory activity (MIA) protein could represent a tool for selecting high risk early stages melanoma patients.Method. Between 2008 and 2013, 155 patients with CMM were treated in our clinic. 84 of them were classified into stages I and II, according to TNM 2009. MIA serum concentration was measured in all patients and 50 healthy donors. A cut-off value of 9.4 ng/ml was established using the ROC curve.Results. All patients were followed up by periodic investigations every 6 months. We have noticed that 66% of patients with MIA serum values at diagnosis greater than 9.4 ng/mL have relapsed, while only 5% of patients with MIA serum concentration below the estimated threshold, recurred during the follow-up period(P=0.000). The death risk was 12 times higher in pathological MIA group of patients(P=0.0001).Conclusions. Our data suggest that MIA is an independent prognostic factor for patients with localized CMM.


2009 ◽  
Vol 31 (6) ◽  
pp. 415-422
Author(s):  
Simone Kaufmann ◽  
Silke Kuphal ◽  
Thomas Schubert ◽  
Anja K. Bosserhoff

Background: Malignant melanoma cells are known to have altered expression of genes supporting proliferation and invasion, however, the expression of molecules of the Netrin family of repellent factors has not been analyzed in melanomas until now.Results: Here, we show that Netrin-1 expression is strongly induced in melanoma cells compared to melanocytes in vivo and in vitro controlled at the transcriptional level via ETS-1. In addition, the expression of the netrin receptor UNC5B was induced and that of UNC5C was reduced in the tumor cells. In order to determine the functional relevance of Netrin-1 expression in malignant melanoma, Netrin expression in melanoma cells was reduced by siRNA attempts and primary human melanocytes were treated with recombinant Netrin-1. The cells showed no changes in proliferation or apoptosis, however, a strong reduction of migratory properties was observed in the melanoma cells after reduction of Netrin expression whereas melanocyte migration was strongly induced by treatment with Netrin.Conclusions: Our study suggests that Netrin-1 promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma.


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