RESUMEN

BACKGROUND: The heat shock protein H11 is silenced in melanoma cell lines, where its forced expression by demethylation with Aza-C triggers apoptosis. OBJECTIVE: To examine whether H11 is silenced by aberrant DNA methylation in melanoma as compared to nevi and normal skin tissues. METHODS: Cell suspensions from benign intradermal nevi, atypical nevi and malignant melanoma tissues were used in reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues were stained with H11 antibody. RESULTS: H11 is methylated in 60-75% of melanoma and atypical nevi, but not in normal skin or most benign nevi. Methylation is inversely correlated with H11 expression. CONCLUSION: The heat shock protein H11 is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic lesions or normal skin melanocytes. The data suggest that H11 is a promising target for the molecular therapy of melanoma.

Asunto(s)

Metilación de ADN , Proteínas de Choque Térmico/genética , Melanocitos/patología , Melanoma/genética , Proteínas Serina-Treonina Quinasas/genética , Neoplasias Cutáneas/genética , Apoptosis , Síndrome del Nevo Displásico/genética , Síndrome del Nevo Displásico/metabolismo , Síndrome del Nevo Displásico/patología , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Humanos , Técnicas para Inmunoenzimas , Melanocitos/metabolismo , Melanoma/metabolismo , Melanoma/patología , Chaperonas Moleculares , Nevo Intradérmico/genética , Nevo Intradérmico/metabolismo , Nevo Intradérmico/patología , Nevo Pigmentado/genética , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patología , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología