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Aberrant methylation of integrin α4 gene in human gastric cancer cells

Oncogene volume 23, pages 3474–3480 (2004)Cite this article

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.

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Acknowledgements

This work was supported in part by grants from the Ministry of Science & Technology of Korea through the National Research Laboratory Program for Cancer Epigenetics and by 2003 BK21 Project for Medicine, Dentistry and Pharmacy. We thank other lab members for helpful discussions and Tae Young Kim for quantitative real-time PCR.

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Authors and Affiliations

  1. National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Jinah Park, Sang-Hyun Song, Tai Young Kim, Moon-Chang Choi, Hyun-Soon Jong, Tae-You Kim, Jung Weon Lee & Yung-Jue Bang

  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Tae-You Kim, Noe Kyeong Kim & Yung-Jue Bang

  3. Department of Pathology, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Woo-Ho Kim

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  1. Jinah Park
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Correspondence to Yung-Jue Bang.

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Park, J., Song, SH., Kim, T. et al. Aberrant methylation of integrin α4 gene in human gastric cancer cells. Oncogene 23, 3474–3480 (2004). https://doi.org/10.1038/sj.onc.1207470

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