Comparative Expression of NFkappaB Proteins in Melanocytes of Normal Skin vs. Benign Intradermal Naevus and Human Metastatic Melanoma Biopsies
| Autor: | Dazhi Cen, Sun Yang, Susan E. McNulty, Raul del Rosario, Frank L. Meyskens |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytoplasm
Biopsy Clinical Biochemistry Transcription Factor RelA Apoptosis Plant Science Biology Phosphoserine NF-KappaB Inhibitor alpha medicine Humans Nevus Melanoma Skin Cell Nucleus medicine.diagnostic_test NF-kappa B Cell Biology medicine.disease NFKB1 Immunohistochemistry Cell nucleus medicine.anatomical_structure Immunology Cancer research Melanocytes Nevus Intradermal I-kappa B Proteins Signal transduction Agronomy and Crop Science Signal Transduction Developmental Biology |
| Zdroj: | Pigment Cell Research. 17:173-180 |
| ISSN: | 1600-0749 0893-5785 |
| DOI: | 10.1111/j.1600-0749.2004.00128.x |
| Popis: | Nuclear factor kappa B (NFkappaB) is an essential regulator of gene transcription for hundreds of genes, including many critically involved in apoptosis. NFkappaB complexes containing cRel generally activate pro-apoptotic genes, while those with RelA activate anti-apoptotic genes. We have previously shown that NFkappaB binding by RelA is constitutively elevated in human metastatic melanoma cultures relative to normal melanocytes. Here we extended our investigation to immunohistochemical analysis of human tissue biopsies. We found that RelA expression is significantly elevated in melanocytes of human naevi and melanomas relative to normal skin, but expression of its inhibitor IkappaB-alpha is significantly lower in metastatic melanomas than in intradermal naevi. Antibodies specific for the nuclear localization signal of RelA also showed significantly increased staining in metastatic melanoma biopsies. Notably, in melanomas and in naevi, we also found that RelA is phosphorylated at serine 529, and this activated form accumulates in the nuclei of melanomas. This suggests that increased expression and phosphorylation of RelA occurs at the stage of the benign naevus, but IkappaB-alpha is able to sequester RelA in the cytoplasm and regulate RelA transcriptional transactivation. We also found that antibodies against cRel show a progressive increase in staining from naevi to melanoma. However, staining for IkappaB-epsilon, which primarily inhibits the nuclear localization of cRel was also progressively increased, and cRel expression was predominantly cytoplasmic in melanomas. These results confirm that the altered expression of RelA found in metastatic melanoma cells in tissue culture is relevant to human tumors and offer new insights into the deregulation of NFkappaB signaling. |
| Databáze: | OpenAIRE |
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