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Clinical and Biological Significance of Hepsin Overexpression in Breast Cancer
  1. Peng Xing, MD*,
  2. Ji-guang Li, MD*†,
  3. Feng Jin, MD*,
  4. Ting-ting Zhao, MD*,
  5. Qun Liu, MD*,
  6. Hui-ting Dong, MD*,
  7. Xiao-lin Wei, MD*
  1. From the *Department of Surgical Oncology, Breast Surgery, General Surgery, First Affiliated Hospital of China Medical University, Shenyang, China; †Cancer Institute of China Medical University, Shenyang, China.
  1. Received December 28, 2010, and in revised form January 29, 2011.
  2. Accepted for publication February 1, 2011.
  3. Reprints: Ji-guang Li, MD, Breast Surgery, Department of Surgical Oncology, General Surgery, First Affiliated Hospital of China Medical University, Shenyang 110001, China. E-mail: jiguangli2010{at}gmail.com.

Abstract

Objective Although many studies have documented the tumor-promoting role of hepsin in several types of malignancies, little is known about its clinical and biological significance in breast cancer.

Materials and Methods Hepsin expression was examined in 4 pairs of fresh breast tumor samples and corresponding nontumor breast tissues by Western blotting. Immunohistochemistry for hepsin was performed on an additional cohort of 215 archival breast cancer samples. The clinical significance of hepsin expression was analyzed. Knockdown of hepsin expression was performed in 2 breast cancer cell lines, MDA-MB-231 and HER18, with a high abundance of endogenous hepsin, and the effects of hepsin silencing on cell invasion and proliferation were evaluated.

Results Hepsin was aberrantly overexpressed in breast cancer tissues relative to adjacent nontumor tissues. Its overexpression was significantly associated with tumor stage (P = 0.037), lymph node metastasis (P = 0.010), estrogen receptor positivity (P = 0.019), and progesterone receptor positivity (P < 0.0001) in patients with breast cancer. Down-regulation of hepsin expression by small interfering RNA (siRNA) significantly reduced cell proliferation and invasion in both the MDA-MB-231 and HER18 cells compared to nonspecific control small interference RNA.

Conclusion Our data demonstrate that hepsin expression is frequently up-regulated in breast cancer tissues, which is associated with tumor growth and progression. Thus, inhibition of hepsin expression might be of therapeutic significance.

Key Words
  • breast cancer
  • hepsin
  • invasion
  • proliferation
  • clinical significance

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