TY - JOUR
T1 - Aberrant DNA methylation of integrin α4
T2 - A potential novel role for metastasis of cholangiocarcinoma
AU - Uhm, Kyung Ok
AU - Lee, Jung Ok
AU - Lee, Yun Mi
AU - Lee, Eun Soo
AU - Kim, Hyeon Soo
AU - Park, Sun Hwa
N1 - Funding Information:
Intrahepatic CC tissues were collected from 29 resected specimens. The specimens were supported by the Liver Cancer Specimen Bank from the National Research Resource Bank Program (The Korea Science and Engineering Foundation in the Ministry of Science and Technology). Institutional review board approval and informed consent were obtained. CC tissues and their corresponding non-CCs were sampled from snap-frozen liver tissues in liquid nitrogen and stored at ¡70°C. The patients in this study included 24 males and 5 females ranging in age from 36 to 73 years (mean § SD, 57 § 10.42 years). As controls, 15 normal liver tissue specimens were obtained from livers resected for benign lesions from ten male and Wve female patients ranging in age from 33 to 67 years (mean § SD, 55 § 11.53 years).
Funding Information:
Acknowledgments This study was supported by the Korea University College of Medicine Grant.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - Purpose Although the altered expression of integrin α4 is known to be associated with transformation or metastasis in several human cancers, the information on cholangiocarcinoma (CC) is still poor. In this study, we investigated the promoter methylation status of integrin α4 gene in CC. Methods A total of 29 CC, 19 adjacent non-tumor-containing tissue and 15 normal liver specimens were used for identification of gene methylation status by methylationspecific polymerase chain reaction. Results The frequency of DNA methylation was 55.17% (16 of 29) in the CC specimens (P < 0.001). Also, transcripts of the integrin α4 gene were decreased in all CC tissues in which there was DNA methylation of the integrin α4 gene. In addition, the downregulated expression of integrin α4 in CC cells with hypermethylation of the integrin α4 gene was restored by treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor. Moreover, we found that DNA methylation of integrin α4 was detected in all CC tissues obtained from patients with LN metastasis (7/7). Furthermore, phosphorylation of paxillin, cell migration-related molecule, was regulated by silencing of integrin α4. Conclusions Taken together, these results suggest that loss of the integrin α4 gene is caused by aberrant DNA methylation of the 5'-CpG island site of the gene, and methylation of the integrin α4 gene can be a useful marker of metastasis of CC.
AB - Purpose Although the altered expression of integrin α4 is known to be associated with transformation or metastasis in several human cancers, the information on cholangiocarcinoma (CC) is still poor. In this study, we investigated the promoter methylation status of integrin α4 gene in CC. Methods A total of 29 CC, 19 adjacent non-tumor-containing tissue and 15 normal liver specimens were used for identification of gene methylation status by methylationspecific polymerase chain reaction. Results The frequency of DNA methylation was 55.17% (16 of 29) in the CC specimens (P < 0.001). Also, transcripts of the integrin α4 gene were decreased in all CC tissues in which there was DNA methylation of the integrin α4 gene. In addition, the downregulated expression of integrin α4 in CC cells with hypermethylation of the integrin α4 gene was restored by treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor. Moreover, we found that DNA methylation of integrin α4 was detected in all CC tissues obtained from patients with LN metastasis (7/7). Furthermore, phosphorylation of paxillin, cell migration-related molecule, was regulated by silencing of integrin α4. Conclusions Taken together, these results suggest that loss of the integrin α4 gene is caused by aberrant DNA methylation of the 5'-CpG island site of the gene, and methylation of the integrin α4 gene can be a useful marker of metastasis of CC.
KW - Cholangiocarcinoma
KW - DNA methylation
KW - Integrin alpha4
KW - Metastasis
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U2 - 10.1007/s00432-009-0646-9
DO - 10.1007/s00432-009-0646-9
M3 - Article
C2 - 19655168
AN - SCOPUS:74049094447
VL - 136
SP - 187
EP - 194
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 2
ER -
