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LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients

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Abstract

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal–epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2007-0056092), and a research grant from National Cancer Center (1110490). Preparation of the final manuscript was done with the assistance of BioScience Writers LLC (Houston, TX). The authors acknowledge Dr. Janine T Erler for advice on studying LOXL2-siRNA. The authors thank Mr. Dong-Su Jang, Research Assistant, Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea, for his help with the figures.

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Authors and Affiliations

  1. Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul, Republic of Korea

    Sung Gwe Ahn, Hak Min Lee, Joon Jeong & Hy-De Lee

  2. Department of Microbiology, Yonsei University Medical College, Seoul, Republic of Korea

    Seung-hyun Kwon & Jae Myun Lee

  3. Department of Microbiology, Brain Korea 21 Project for Medical Sciences, Yonsei University Medical College, 250 Seongsanno, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Jae Myun Lee

  4. Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea

    Seung Myung Dong & Ji-hae Lee

  5. Cha Research Institute, Cha University, Seoul, Republic of Korea

    Akira Oshima

  6. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Woo Ho Kim

  7. Department of Surgery, Eulji University College of Medicine, Seoul, Republic of Korea

    Seung Ah Lee

  8. Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jeffrey E. Green

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  1. Sung Gwe Ahn
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  9. Jae Myun Lee
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Correspondence to Jae Myun Lee or Joon Jeong.

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Sung Gwe Ahn and Seung Myung Dong contributed equally to this work.

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Ahn, S.G., Dong, S.M., Oshima, A. et al. LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients. Breast Cancer Res Treat 141, 89–99 (2013). https://doi.org/10.1007/s10549-013-2662-3

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  • DOI: https://doi.org/10.1007/s10549-013-2662-3

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