Hs.137007 is a novel epigenetic marker hypermethylated and up-regulated in breast cancer.
This study was conducted to mine novel breast-specific unigenes and analyze their epigenetic regulation in breast cancer. Differential digital display and methylation analysis identified the Hs.137007 gene containing a Kelch domain as a candidate novel epigenetic marker. In 50 pairs of breast cancer tissues and nearby normal tissues the methylation level of the 14 CpG sites at the promoter region (-778 to -485) of the gene was higher in cancer tissues (72-93%) than in normal tissues (31-83%), with a high correlation rate (p<0.05). End-point RT-PCR and real-time RT-PCR revealed that Hs.137007 was up-regulated in cancer tissues. A clear relationship between high methylation levels and up-regulated expression was also observed in the cultured breast cell lines. The MCF7 (90-100%) and MDAMB468 (100%) cancer cell lines that showed higher methylation than the BT549 (20-90%) and 184B5 (10-100%) at the 14 CpGs also showed elevated gene expression. Taken together, these results indicate that the Hs.137007 gene is a novel gene specifically expressed in the breast that can be utilized as an epigenetic marker of breast cancer.
Kim
Tae Woo
TW
Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715, Korea.
Kim
Yoo Jung
YJ
Lee
Hyun Ji
HJ
Min
Sun Young
SY
Kang
Han-Sung
HS
Kim
Sun Jung
SJ
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015854:Up-Regulation
D014408:Biomarkers, Tumor