Article ; Online: Ring finger protein 6 promotes breast cancer cell proliferation by stabilizing estrogen receptor alpha.
2017 Volume 8, Issue 12, Page(s) 20103–20112
Abstract: Ring finger protein 6 (RNF6) is a key oncogene in both prostate cancer and leukemia, but its role ... exists an RNF6/ERα/Bcl-xL axle in breast cancer which promotes cancer cell proliferation and survival ... In doxorubicin-resistant breast cancer cells, RNF6 was found to be elevated in association with increased ERα and ...
| Abstract | 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 ERα expression and increased its stability. In doxorubicin-resistant breast cancer cells, RNF6 was found to be elevated in association with increased ERα and anti-apoptotic Bcl-xL, but not pro-apoptotic Bim-1. In consistence with this finding, overexpression of ERα led to increased Bcl-xL but had no effects on Bim-1. Therefore, this study demonstrated that there exists an RNF6/ERα/Bcl-xL axle in breast cancer which promotes cancer cell proliferation and survival. Targeting the RNF6/ERα/Bcl-xL axle could be a promising strategy in the treatment of breast cancer. |
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| MeSH term(s) | Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/secondary ; Case-Control Studies ; Cell Proliferation ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Survival Rate ; Tumor Cells, Cultured ; bcl-X Protein/genetics ; bcl-X Protein/metabolism |
| Chemical Substances | BCL2L1 protein, human ; Biomarkers, Tumor ; DNA-Binding Proteins ; Estrogen Receptor alpha ; RNF6 protein, human ; bcl-X Protein |
| Language | English |
| Publishing date | 2017-03-21 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2560162-3 |
| ISSN | 1949-2553 ; 1949-2553 |
| ISSN (online) | 1949-2553 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.15384 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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