| Title |
AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer
|
|---|---|
| Published in |
Molecular Cancer, September 2018
|
| DOI | 10.1186/s12943-018-0883-0 |
| Pubmed ID | |
| Authors |
Lu Cao, Cong Xu, Guomin Xiang, Fang Liu, Xiaozhen Liu, Congying Li, Jing Liu, Qingxiang Meng, Jiao Jiao, Yun Niu |
| Abstract |
Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear. AR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR-PDEF-MAD1-MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo. We found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo. Our data highlight the role of the AR-PDEF-MAD1-MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| France | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 18% |
| Student > Bachelor | 4 | 18% |
| Librarian | 2 | 9% |
| Other | 1 | 5% |
| Student > Doctoral Student | 1 | 5% |
| Other | 2 | 9% |
| Unknown | 8 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
| Biochemistry, Genetics and Molecular Biology | 2 | 9% |
| Psychology | 2 | 9% |
| Medicine and Dentistry | 2 | 9% |
| Agricultural and Biological Sciences | 1 | 5% |
| Other | 4 | 18% |
| Unknown | 9 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2018.
All research outputs
#14,362,166
of 23,103,436 outputs
Outputs from Molecular Cancer
#903
of 1,740 outputs
Outputs of similar age
#187,889
of 337,432 outputs
Outputs of similar age from Molecular Cancer
#17
of 38 outputs
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