Hypomethylation of the interleukin-10 gene in breast cancer tissues.
The purpose of the study was to evaluate the methylation status of the interleukin-10 (IL-10) gene in breast cancer tissues compared with normal and benign breast disease tissues. Between 2000 and 2001, we used paraffin-embedded specimens of 30 normal, 31 benign and 72 breast cancer tissues from the National Cancer Center, Korea. The methylation patterns of the IL-10 gene were evaluated using bisulfite DNA sequencing and the expression levels of IL-10 mRNA were evaluated using real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). The methylation rates of the IL-10 gene were significantly lower in malignant tumors than in benign and normal tissues (normal; 63.3%, benign; 74.2%, cancer; 45.8%, p = 0.02). The methylation density rates of the IL-10 gene were also significantly lower in malignant tumors (normal; 59.68 ± 7.12%, benign; 48.89 ± 7.45%, cancer; 30.56 ± 4.18%, p = 0.001). Tissues with aberrant methylation of the IL-10 gene showed significantly lower rates of mRNA expression compared with unmethylated cases (12.5% vs. 68.0%, p = 0.012). The mRNA expression of tissues with unmethylated IL-10 was upregulated approximately ten thousand-fold compared to those with IL-10 methylation in the real-time RT-PCR experiment. IL-10 methylation demonstrated a significant association with lower expression of Ki-67 (9.36 ± 2.43 vs. 19.68 ± 3.42, p = 0.02). IL-10 methylation in cancer tissues is lower than that in normal and benign breast tissues, and DNA hypomethylation in the gene influences gene activation. Our data suggest that hypomethylation of the IL-10 gene can be involved in the process of breast carcinogenesis.
Son
Keun Su
KS
Department of Life Science, Dongguk University, Seoul 100-715, South Korea.
Kang
Han-Sung
HS
Kim
Sun Jung
SJ
Jung
So-Youn
SY
Min
Sun Young
SY
Lee
See Youn
SY
Kim
Seok Won
SW
Kwon
Youngmee
Y
Lee
Keun Seok
KS
Shin
Kyung Hwan
KH
Ro
Jungsil
J
D000704:Analysis of Variance; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D019394:Ki-67 Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D019394:Ki-67 Antigen; D012333:RNA, Messenger; D016753:Interleukin-10