Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatin
Resistance to various anti-neoplastic agents is a common observation in clinical management of melanoma. The biologic mechanisms conferring these different drug-resistant phenotypes, including resistance against the commonly used anti-cancer drug cisplatin, are unclear. In order to elucidate the rol...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 December 2015
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| In: |
The journal of investigative dermatology
Year: 2003, Volume: 121, Issue: 1, Pages: 172-176 |
| ISSN: | 1523-1747 |
| DOI: | 10.1046/j.1523-1747.2003.12313.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1046/j.1523-1747.2003.12313.x Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X15303080 
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| Author Notes: | Bernd Liedert, Verena Materna, Dirk Schadendorf, Jürgen Thomale, Hermann Lage |
| Summary: | Resistance to various anti-neoplastic agents is a common observation in clinical management of melanoma. The biologic mechanisms conferring these different drug-resistant phenotypes, including resistance against the commonly used anti-cancer drug cisplatin, are unclear. In order to elucidate the role of the membrane adenosine triphosphate binding cassette-transporter cMOAT (canalicular multispecific anion transporter) (MRP2/ABCC2) in cisplatin resistance of melanoma, the expression of this protein was analyzed in the platinum drug-resistant cell line MeWo CIS 1. Cisplatinresistant melanoma cells showed a distinct overexpression of cMOAT on mRNA and protein level. This observation was accompanied by a reduced formation of platinum-induced intrastrand cross-links in the nuclear DNA measured by an immunocytologic assay. This decrease in DNA platination was accompanied by an accelerated re-entry into the cell cycle after the typical cisplatin-induced G2 arrest, and a resistance to undergo apoptosis. Kinetics of formation and elimination of platinum-DNA adducts suggest that the DNA repair capacity for Pt-d(GpG) adducts was not elevated in platinum drug-resistant melanoma cells. The decrease in platinum-DNA adduct formation in cisplatin-resistant melanoma cells was rather a reflection of the protecting activity of the transporter cMOAT. In conclusion, the functional inhibition of cMOAT might be a promising strategy in the reversal of resistance to platinum-based anti-cancer drugs in human melanoma. |
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| Item Description: | Elektronische Reproduktion der Druckausgabe Im Titel ist die Zahl 2 im Ausdruck "G2-arrest" tiefgestellt Gesehen am 23.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1523-1747 |
| DOI: | 10.1046/j.1523-1747.2003.12313.x |