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


CONCLUSIONS
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.
Sharma
B K
BK
Virology/Immunology Laboratories, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Md. 21201, USA.
Smith
Cynthia C
CC
Laing
Jennifer M
JM
Rucker
Dakara A
DA
Burnett
Joseph W
JW
Aurelian
Laure
L
D017209:Apoptosis; D019175:DNA Methylation; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018832:Molecular Chaperones; D018330:Nevus, Intradermal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases