Aberrant methylation of integrin α4 gene in human gastric cancer cells

Jinah Park, Sang Hyun Song, Tai Young Kim, Moon Chang Choi, Hyun Soon Jong, Taeyou Kim, Jung Weon Lee, Noe Kyeong Kim, Woo Ho Kim, Yung Jue Bang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin α4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been explored. In the present study, we found that the integrin α4 expression is lost in human gastric cancer cell lines and that this is recovered by treatment with DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. Methylation-specific PCR (MSP) and bisulfite genomic DNA sequencing demonstrated the CpG methylation-dependent silencing of integrin α4 expression in eight of nine (88.8%) gastric cancer cell lines and in 84.7% of 46 primary tumors. We also investigated whether the restoration of integrin α4 in integrin α4-inactivated cells affects their ability to invade extracellular matrix, using matrigel assays. Interestingly, integrin α4-stable transfectants had markedly less invasive ability than the parental cells. Taken together, these results suggest that the transcriptional repression of the integrin α4 gene is caused by aberrant DNA methylation, and that this may play an important role in human gastric carcinogenesis.

Original languageEnglish
Pages (from-to)3474-3480
Number of pages7
JournalOncogene
Volume23
Issue number19
DOIs
StatePublished - 22 Apr 2004

Fingerprint

Integrins
Methylation
Stomach Neoplasms
Genes
DNA Methylation
Extracellular Matrix
Cell Line
Neoplasms
Methyltransferases
DNA Sequence Analysis
Cell Communication
Stomach
Carcinogenesis
Neoplasm Metastasis
Polymerase Chain Reaction
DNA

Keywords

  • Gastric cancer
  • Integrin α4
  • Methylation

Cite this

Park, Jinah ; Song, Sang Hyun ; Kim, Tai Young ; Choi, Moon Chang ; Jong, Hyun Soon ; Kim, Taeyou ; Lee, Jung Weon ; Kim, Noe Kyeong ; Kim, Woo Ho ; Bang, Yung Jue. / Aberrant methylation of integrin α4 gene in human gastric cancer cells. In: Oncogene. 2004 ; Vol. 23, No. 19. pp. 3474-3480.
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Park, J, Song, SH, Kim, TY, Choi, MC, Jong, HS, Kim, T, Lee, JW, Kim, NK, Kim, WH & Bang, YJ 2004, 'Aberrant methylation of integrin α4 gene in human gastric cancer cells', Oncogene, vol. 23, no. 19, pp. 3474-3480. https://doi.org/10.1038/sj.onc.1207470

Aberrant methylation of integrin α4 gene in human gastric cancer cells. / Park, Jinah; Song, Sang Hyun; Kim, Tai Young; Choi, Moon Chang; Jong, Hyun Soon; Kim, Taeyou; Lee, Jung Weon; Kim, Noe Kyeong; Kim, Woo Ho; Bang, Yung Jue.

In: Oncogene, Vol. 23, No. 19, 22.04.2004, p. 3474-3480.

Research output: Contribution to journalArticle

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Park J, Song SH, Kim TY, Choi MC, Jong HS, Kim T et al. Aberrant methylation of integrin α4 gene in human gastric cancer cells. Oncogene. 2004 Apr 22;23(19):3474-3480. https://doi.org/10.1038/sj.onc.1207470