AUTHOR=Kim Yu-Jin , Lee Gyunghwa , Han Jinil , Song Kyoung , Choi Joon-Seok , Choi Yoon-La , Shin Young Kee 

TITLE=UBE2C Overexpression Aggravates Patient Outcome by Promoting Estrogen-Dependent/Independent Cell Proliferation in Early Hormone Receptor-Positive and HER2-Negative Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01574

DOI=10.3389/fonc.2019.01574

ISSN=2234-943X

ABSTRACT=<p>We previously showed that <italic>UBE2C</italic> mRNA expression is significantly associated with poor prognosis only in patients with hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)– breast cancer. In this study, we further reanalyzed the correlation between <italic>UBE2C</italic> mRNA expression and clinical outcomes in patients with HR+/HER2– breast cancer, and we investigated the molecular mechanism underlying the role of UBE2C modulation in disease progression in this subgroup of patients. Univariate and multivariate analyses showed that high <italic>UBE2C</italic> expression was associated with significantly shorter survival of breast cancer patients with pN0 and pN1 tumors but not pN2/N3 tumors (<italic>P</italic> &lt; 0.05). <italic>In vitro</italic> functional experiments in HR+/HER2– breast cancer cells showed that UBE2C expression is a tumorigenic factor, and that estrogen upregulated <italic>UBE2C</italic> mRNA and protein by directly binding to the <italic>UBE2C</italic> promoter region. UBE2C knockdown inhibited cell proliferation by affecting cell cycle progression, and UBE2C overexpression was associated with estrogen-independent growth. UBE2C depletion markedly increased the cytotoxicity of tamoxifen by inducing apoptosis. The present findings suggest that UBE2C overexpression is correlated with relapse and promotes estrogen-dependent/independent proliferation in early HR+/HER2– breast cancer.</p>