Promoter methylation of heat shock protein B2 in human esophageal squamous cell carcinoma.
Hypermethylation of gene promoters and the corresponding loss of gene expression are recognized as a hallmark of human cancer, and DNA methylation has emerged as a promising biomarker for the detection of human esophageal squamous cell carcinoma (ESCC). To identify novel genes methylated in ESCC, we screened 35 candidate genes identified from an oligonucleotide microarray. Among them, the heat shock protein B2 (HSPB2) was methylated in 95.7% (67/70) of primary ESCCs, whereas no methylation was found in normal esophageal tissues from ESCC patients (0%, 0/20). RT-PCR analysis revealed that HSPB2 expression was silenced or weakly expressed in most ESCC cell lines, and re-activated by the demethylating agent 5-aza-2'-deoxy-cytidine. These results indicate that promoter methylation of HSPB2 is one of the causal factors for loss or down-regulation of HSPB2 expression. mRNA expression of HSPB2 in ESCC tissues was significantly down-regulated compared to normal tissues. Our data suggest that promoter methylation of HSPB2 deserves further attention as a novel molecular biomarker in human ESCC.
Department of Otolaryngology, Head and Neck Cancer Research Division, The Johns Hopkins University, School of Medicine, 1550 Orleans Street, CRB II-5M, Baltimore, MD 21231, USA.
Xiaofei
X
Chang
Keishi
K
Yamashita
David
D
Sidransky
Myoung Sook
MS
Kim
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C442250:HSPB2 protein, human
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