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Ring finger protein 6 promotes breast cancer cell proliferation by stabilizing
estrogen receptor alpha
#MMPMID28223545
Zeng Y
; Xu X
; Wang S
; Zhang Z
; Liu Y
; Han K
; Cao B
; Mao X
Oncotarget
2017[Mar]; 8
(12
): 20103-20112
PMID28223545
show ga
Ring finger protein 6 (RNF6) is a key oncogene in both prostate cancer and
leukemia, but its role is elusive in breast cancer. In the present study, we
found that RNF6 was overexpressed in more than 70% of breast cancer tissues and
it was associated with overall survival. RNF6 increased breast cancer cell
proliferation, migration and reduced cell sensitivity to doxorubicin. Further
studies showed that RNF6 was closely associated with increased expression of
estrogen receptor, a critical factor in the development of breast cancers. RNF6
was found to induce ER? expression and increased its stability. In
doxorubicin-resistant breast cancer cells, RNF6 was found to be elevated in
association with increased ER? and anti-apoptotic Bcl-xL, but not pro-apoptotic
Bim-1. In consistence with this finding, overexpression of ER? led to increased
Bcl-xL but had no effects on Bim-1. Therefore, this study demonstrated that there
exists an RNF6/ER?/Bcl-xL axle in breast cancer which promotes cancer cell
proliferation and survival. Targeting the RNF6/ER?/Bcl-xL axle could be a
promising strategy in the treatment of breast cancer.
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