Exceptionally high UBE2C expression is a unique phenomenon in basal-like type breast cancer and is regulated by BRCA1

Abstract

Ubiquitin-conjugating enzyme 2C (UBE2C) is overexpressed in various types of cancer, leading to poor outcomes and drug resistance. UBE2C may also have a critical role in phenotypes associated with poor prognosis in breast cancer; however, the relationship between UBE2C expression and clinical outcome in breast cancer subtypes has not previously been investigated. We firstly analyzed breast cancer patient data and immunohistochemistry of breast cancer patient samples. We demonstrated that UBE2C was associated with poor prognosis in breast cancer, particularly basal-like breast cancer, a subtype with aggressive clinical features. Interestingly, we found that there was a close relationship between the expression of BRCA1 and UBE2C in the MCF-7 and MDA-MB-231 breast cancer cell lines. Upregulation of BRCA1 could inhibit the expression of UBE2C. In cells with BRCA1 silenced down, expression of UBE2C was obviously increased, with a concurrent decrease in cellular sensitivity to doxorubicin. Suppression of UBE2C expression by RNA interference led to decrease the mRNA expressions of BCRP, MRP1 and P-gp in doxorubicin-treated MDA-MB-231 cells. Moreover, treatment with 1μg/ml doxorubicin led to increased expression of UBE2C. The results show high expression of UBE2C is a potential prognostic factor of poor outcome in basal-like breast cancer. Moreover, loss of BRCA1 function results in an increase in UBE2C expression and chemical resistance to doxorubicin in breast cancer cells.

Keywords: BRCA1; Breast cancer; Doxorubicin; UBE2C.