35P - USP2 promotes progression in triple negative breast cancer

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Qing Qu
Citation Annals of Oncology (2014) 25 (suppl_1): i8-i16. 10.1093/annonc/mdu066
Authors Q. Qu1, Y. Mao2, Y.Z. Zhang1, J.J. Liu1, X. Chen1, K.W. Shen1
  • 1Comprehensive Breast Health Center, Ruijin Hospital Shanghai Jiaotong University School of Medicine, 200025 - shanghai/CN
  • 2Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025 - shanghai/CN

Abstract

Background:

The ubiquitin-specific protease 2 (USP2) is a member of the USP family known as deubiquitinating enzymes, which play a critical role in the protection of prostate cancer from apoptosis. Until now, the role of USP2 in breast cancer has not been very clear.

Material and methods:

First, We identified USP2 expression levels in human breast tumors using immunohistochemistry. 121 primary breast cancers, 13 paired normal tissues and 13 paired distant metastatic lesions were assessed. Survival analysis was performed using log-rank test and Cox regression hazard model. Secondly, we performed matrigel migration and invasion assays with USP2-silenced and USP2-overexpressed breast cancer cell lines to understand the basic mechanism. Protein expression was analyzed by western blot.

Results:

In 121 human breast tumors, cytoplasmic positive immunostaining of USP2 was detected in tumorous glands; whereas in normal breast epithelium, its expression was negative. Moreover USP2 was overexpressed in distant metastatic lesion compared with primary breast cancer. More importantly, positive USP2 immunostaining was correlated with the triple negative breast cancer (TNBC) subtype. Survival analyses demonstrated that positive USP2 is a poor prognostic factor for disease-free survival. By in vitro study we found that silencing of USP2 by siRNA decreased migration and invasion in LM2-4175 and SCP46, two metastatic subclones of the TNBC cell line MDA-MB-231, associated with decreased matrix metalloproteinase 2 (MMP2) expression. On the other hand, overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion, and also increased the expression of MMP2.

Conclusions:

These clinical and preclinical data confirm that higher USP2 expression is associated with poorer survival of breast cancer patients and invasiveness of TNBC cells. Our results suggest the clinical value of USP2 as a new therapeutic target in TNBC.