PPAR $\gamma$ regulates MITF and $\beta-catenin$ expression and promotes a differentiated phenotype in mouse melanoma S91
| Autor: | Piotr Laidler, Przemyslaw M. Plonka, Krystyna Urbanska, Krzysztof Reiss, Maja Grabacka, Wojciech Placha |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Blotting Western Mesenchymal cell differentiation Peroxisome proliferator-activated receptor Fluorescent Antibody Technique Antineoplastic Agents Tretinoin Dermatology Biology tyrosinase General Biochemistry Genetics and Molecular Biology Article ciglitazone Mice Melanocyte differentiation Ciglitazone Cell Line Tumor medicine Animals Promoter Regions Genetic Cell Shape Melanoma Alitretinoin beta Catenin chemistry.chemical_classification Microphthalmia-Associated Transcription Factor Monophenol Monooxygenase Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Wnt signaling pathway Cell Differentiation differentiation Microphthalmia-associated transcription factor medicine.disease Molecular biology Antigens Differentiation Up-Regulation Gene Expression Regulation Neoplastic PPAR gamma Phenotype Oncology chemistry spindle morphology Cancer research Melanocytes Thiazolidinediones microphthalmia‐associated transcription factor |
| Popis: | Melanoma represents one of the most rapidly metastasizing, hence deadly tumors due to its high proliferation rate and invasiveness, characteristics of undifferentiated embryonic tissues. Given the absence of effective therapy for metastatic melanoma, understanding more fully the molecular mechanisms underlying melanocyte differentiation may provide opportunities for novel therapeutic intervention. Here we show that in mouse melanoma S91 cells activation of the peroxisome proliferator activated receptor (PPAR) gamma induces events resembling differentiation, such as growth arrest accompanied by apoptosis, spindle morphology and enhanced tyrosinase expression. These events are preceded by an initial transient increase in expression from the Microphthalmia-associated transcription factor gene, (MITF) promoter, whereas exposure to a PPAR gamma ligand- ciglitazone that exceeds 8 h, causes a gradual decrease of MITF, until by 48 h MITF expression is substantially reduced. Beta-catenin, an MITF transcriptional activator, shows a similar pattern of decline during ciglitazone treatment, consistent with previous reports that activated PPAR gamma inhibits the Wnt/beta-catenin pathway through induction of beta-catenin proteasomal degradation. We suggest that the PPAR gamma-mediated beta-catenin down-regulation is likely to be responsible for changes in MITF levels. The data suggest that PPAR gamma, besides its well-established role in mesenchymal cell differentiation towards adipocytes, might regulate differentiation in the melanocytic lineage. |
| Databáze: | OpenAIRE |
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