Sharma B K, Smith Cynthia C, Laing Jennifer M, Rucker Dakara A, Burnett Joseph W, Aurelian Laure
Virology/Immunology Laboratories, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Md. 21201, USA.
Dermatology. 2006;213(3):192-9. doi: 10.1159/000095035.
The heat shock protein H11 is silenced in melanoma cell lines, where its forced expression by demethylation with Aza-C triggers apoptosis.
To examine whether H11 is silenced by aberrant DNA methylation in melanoma as compared to nevi and normal skin tissues.
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.
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.
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.
热休克蛋白H11在黑色素瘤细胞系中沉默,用5-氮杂胞苷去甲基化强制其表达可触发细胞凋亡。
研究与痣和正常皮肤组织相比,H11在黑色素瘤中是否因异常DNA甲基化而沉默。
将来自良性真皮内痣、非典型痣和恶性黑色素瘤组织的细胞悬液用于逆转录聚合酶链反应和甲基化特异性聚合酶链反应。石蜡包埋组织用H11抗体染色。
60%-75%的黑色素瘤和非典型痣中H11发生甲基化,但正常皮肤或大多数良性痣中未发生甲基化。甲基化与H11表达呈负相关。
热休克蛋白H11在黑色素瘤中因异常DNA甲基化而沉默,但在良性黑素细胞病变或正常皮肤黑素细胞中未沉默。数据表明H11是黑色素瘤分子治疗的一个有前景的靶点。