Aberrant DNA methylation silences the novel heat shock protein H11 in melanoma but not benign melanocytic lesions

Dermatology. 2006;213(3):192-9. doi: 10.1159/000095035.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • DNA Methylation*
  • Dysplastic Nevus Syndrome / genetics
  • Dysplastic Nevus Syndrome / metabolism
  • Dysplastic Nevus Syndrome / pathology
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Melanocytes / metabolism
  • Melanocytes / pathology*
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Molecular Chaperones
  • Nevus, Intradermal / genetics
  • Nevus, Intradermal / metabolism
  • Nevus, Intradermal / pathology
  • Nevus, Pigmented / genetics
  • Nevus, Pigmented / metabolism
  • Nevus, Pigmented / pathology
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology

Substances

  • HSPB8 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Protein Serine-Threonine Kinases