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Aberrant DNA methylation of integrin α4 in human breast cancer

  • Research Article
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Tumor Biology

Abstract

Integrins are cell surface receptors that mediate cell–cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.

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Acknowledgements

This study was supported by the Samsung Biomedical Research Institute grant, #SBRI C-B0-319-2.

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Authors and Affiliations

  1. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    Sung-Im Do

  2. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine Suwon, Suwon, Korea

    Eunkyung Ko & Duk-Hwan Kim

  3. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong, Kangnam-gu, Seoul, 135-710, South Korea

    So Young Kang & Eun Yoon Cho

  4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Jeong Eon Lee & Seok Jin Nam

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  1. Sung-Im Do
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  2. Eunkyung Ko
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  3. So Young Kang
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  4. Jeong Eon Lee
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  5. Seok Jin Nam
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  7. Duk-Hwan Kim
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Correspondence to Eun Yoon Cho.

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Cite this article

Do, SI., Ko, E., Kang, S.Y. et al. Aberrant DNA methylation of integrin α4 in human breast cancer. Tumor Biol. 35, 7079–7084 (2014). https://doi.org/10.1007/s13277-014-1952-7

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  • DOI: https://doi.org/10.1007/s13277-014-1952-7

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