Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 187-194 |
| Number of pages | 8 |
| Journal | Journal of Cancer Research and Clinical Oncology |
| Volume | 136 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2010 Feb 1 |
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Keywords
- Cholangiocarcinoma
- DNA methylation
- Integrin alpha4
- Metastasis
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Aberrant DNA methylation of integrin α4 : A potential novel role for metastasis of cholangiocarcinoma. / Uhm, Kyung Ok; Lee, Jung Ok; Lee, Yun Mi; Lee, Eun Soo; Kim, Hyeon Soo; Park, Sun-Hwa.
In: Journal of Cancer Research and Clinical Oncology, Vol. 136, No. 2, 01.02.2010, p. 187-194.Research output: Contribution to journal › Article
}
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
PY - 2010/2/1
Y1 - 2010/2/1
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
UR - http://www.scopus.com/inward/record.url?scp=74049094447&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74049094447&partnerID=8YFLogxK
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 -