Ubiquitin-Conjugating Enzyme UBE2C Is Highly Expressed in Breast Microcalcification Lesions

Chen-Pin Chou,Jiin-Tsuey Cheng,Chian-Feng Chen,Nan-Jing Peng,Tsung-Hsien Chang,Jih-Jung Chen,Huay-Ben Pan,Shu-Jhen Jhuang,Nan-Chieh Huang,William B Coleman

doi:10.1371/journal.pone.0093934

Abstract

Ubiquitin-conjugating enzyme 2C (UBE2C) contributes to ubiquitin-mediated proteasome degradation of cell cycle progression in breast cancer. Microcalcification (MC) is the most common mammographic feature of early breast cancer. In this study, we evaluated whether UBE2C could be a tumor marker of early breast cancer with MC found on screening mammography. UBE2C protein and mRNA expression were measured in breast core biopsy pairs of MC and adjacent non-MC breast tissue from each subject. Immunohistochemistry revealed UBE2C positivity in 69.4% of MC samples and 77.6% negativity in non-MC samples (p<0.0001). On RT-qPCR, 56.1% of malignant MC lesion samples showed high mRNA level of UBE2C and 80% of benign MC lesion samples showed a low level of UBE2C (p = 0.1766). We investigated the carcinogenic role of UBE2C in MCF-7 breast cancer cells with UBE2C knockdown; UBE2C knockdown downregulated cell proliferation and activated the cellular apoptosis pathway to inhibit cell colony formation. Furthermore, UBE2C expression was associated with that of carcinogenic genes human epidermal growth factor receptor type 2 (HER2), cellular c-Ki-ras2 proto-oncogene (KRAS), vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), C-C motif chemokine 5 (CCL5), neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and Ras homolog family member C (RhoC). UBE2C may be a marker for diagnosis of nonpalpable breast lesions but not benign or malignant tumors in mammography core biopsies. Suppression of UBE2C may be a potential therapy target in breast cancer.

Highlights

Breast cancer represents the highest cancer incidence rate and the fourth highest mortality rate for women in Taiwan [1,2]
Ubiquitin-conjugating enzyme 2C (UBE2C) is required for breast cancer cell growth Because we found that UBE2C induction might play a role in breast lesions, the link with malignant tumor progression was ambiguous, we investigated the carcinogenic role of UBE2C in the human breast cancer cell lines MCF-7 and MDA-MB-231
Core biopsy specimens of breast lesions can be obtained for cancer histology diagnosis and cancer biomarker analysis [8]

Summary

Introduction

Breast cancer represents the highest cancer incidence rate and the fourth highest mortality rate for women in Taiwan [1,2]. Diagnosis and proper treatment are critical in patient survival [3,4,5]. Several tests performed to stage breast cancer include biopsy and imaging tests such as chest x-ray, mammography, bone scan, CT and MRI [6]. Mammography is the most important imaging tool for the detection and diagnosis of breast cancer, for non-invasive ductal carcinoma in situ (DCIS) breast cancer [7]. Screening mammography can detect early, nonpalpable breast cancer, because as many as 2% of all screened women will undergo biopsy, yielding a positive biopsy rate of about 25% and improved long-term survival and cure rate [8]. More than half of the breast cancer cases found were at highly curable stage 0 and 1 [2]

Methods

Results

Conclusion