Aberrant DNA methylation of integrin α4: A potential novel role for metastasis of cholangiocarcinoma

Kyung Ok Uhm, Jung Ok Lee, Yun Mi Lee, Eun Soo Lee, Hyeon Soo Kim, Sun-Hwa Park

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish
Pages (from-to)187-194
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume136
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Fingerprint

Cholangiocarcinoma
DNA Methylation
Integrins
Neoplasm Metastasis
Genes
Methylation
decitabine
Paxillin
CpG Islands
Methyltransferases
Cell Movement
Down-Regulation
Phosphorylation
Polymerase Chain Reaction

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 journalArticle

@article{53fd72c04a84412db80820db63b4fc0d,
title = "Aberrant DNA methylation of integrin α4: A potential novel role for metastasis of cholangiocarcinoma",
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.",
keywords = "Cholangiocarcinoma, DNA methylation, Integrin alpha4, Metastasis",
author = "Uhm, {Kyung Ok} and Lee, {Jung Ok} and Lee, {Yun Mi} and Lee, {Eun Soo} and Kim, {Hyeon Soo} and Sun-Hwa Park",
year = "2010",
month = "2",
day = "1",
doi = "10.1007/s00432-009-0646-9",
language = "English",
volume = "136",
pages = "187--194",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "2",

}

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 -