乳腺癌中 hepsin 过表达的临床和生物学意义。

Clinical and biological significance of hepsin overexpression in breast cancer.

机构信息

Department of Surgical Oncology, Breast Surgery, General Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

J Investig Med. 2011 Jun;59(5):803-10. doi: 10.2310/JIM.0b013e31821451a1.

DOI:10.2310/JIM.0b013e31821451a1

PMID:21383634

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.

摘要

目的

尽管许多研究已经证实了组织蛋白酶 H 在几种类型的恶性肿瘤中的促肿瘤作用，但关于其在乳腺癌中的临床和生物学意义知之甚少。

材料和方法

通过 Western blot 检测 4 对新鲜乳腺癌肿瘤样本及其相应非肿瘤乳腺组织中组织蛋白酶 H 的表达。对另外 215 例存档乳腺癌样本进行组织蛋白酶 H 的免疫组织化学检测。分析组织蛋白酶 H 表达的临床意义。在具有高丰度内源性组织蛋白酶 H 的 2 种乳腺癌细胞系 MDA-MB-231 和 HER18 中，敲低组织蛋白酶 H 的表达，并评估组织蛋白酶 H 沉默对细胞侵袭和增殖的影响。

结果

与相邻非肿瘤组织相比，组织蛋白酶 H 在乳腺癌组织中异常过表达。其过表达与肿瘤分期（P=0.037）、淋巴结转移（P=0.010）、雌激素受体阳性（P=0.019）和孕激素受体阳性（P<0.0001）显著相关。与非特异性对照小干扰 RNA 相比，小干扰 RNA（siRNA）下调组织蛋白酶 H 的表达显著降低了 MDA-MB-231 和 HER18 细胞的增殖和侵袭能力。