| Title |
Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, August 2014
|
| DOI | 10.1007/s10549-014-3098-0 |
| Pubmed ID | |
| Authors |
Bharath Rudraraju, Marjolein Droog, Tarek M. A. Abdel-Fatah, Wilbert Zwart, Athina Giannoudis, Mohammed I. Malki, David Moore, Hetal Patel, Jacqui Shaw, Ian O. Ellis, Steve Chan, Greg N. Brooke, Ekaterina Nevedomskaya, Christiana Lo Nigro, Jason Carroll, R. Charles Coombes, Charlotte Bevan, Simak Ali, Carlo Palmieri |
| Abstract |
Activating transcription factor-2 (ATF-2) has been implicated as a tumour suppressor in breast cancer (BC). c-JUN N-terminal kinase (JNK) and p38 MAPK phosphorylate ATF-2 within the activation domain (AD), which is required for its transcriptional activity. To date, the role of ATF-2 in determining response to endocrine therapy has not been explored. Effects of ATF-2 loss in the oestrogen receptor (ER)-positive luminal BC cell line MCF7 were explored, as well as its role in response to tamoxifen treatment. Genome-wide chromatin binding patterns of ATF-2 when phosphorylated within the AD in MCF-7 cells were determined using ChIP-seq. The expression of ATF-2 and phosphorylated ATF-2 (pATF-2-Thr71) was determined in a series of 1,650 BC patients and correlated with clinico-pathological features and clinical outcome. Loss of ATF-2 diminished the growth-inhibitory effects of tamoxifen, while tamoxifen treatment induced ATF-2 phosphorylation within the AD, to regulate the expression of a set of 227 genes for proximal phospho-ATF-2 binding, involved in cell development, assembly and survival. Low expression of both ATF-2 and pATF-2-Thr71 was significantly associated with aggressive pathological features. Furthermore, pATF-2 was associated with both p-p38 and pJNK1/2 (< 0.0001). While expression of ATF-2 is not associated with outcome, pATF-2 is associated with longer disease-free (p = 0.002) and BC-specific survival in patients exposed to tamoxifen (p = 0.01). Furthermore, multivariate analysis confirmed pATF-2-Thr71 as an independent prognostic factor. ATF-2 is important for modulating the effect of tamoxifen and phosphorylation of ATF-2 within the AD at Thr71 predicts for improved outcome for ER-positive BC receiving tamoxifen. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 4% |
| Unknown | 24 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 24% |
| Researcher | 4 | 16% |
| Other | 3 | 12% |
| Student > Master | 3 | 12% |
| Professor | 2 | 8% |
| Other | 4 | 16% |
| Unknown | 3 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 9 | 36% |
| Medicine and Dentistry | 4 | 16% |
| Biochemistry, Genetics and Molecular Biology | 3 | 12% |
| Social Sciences | 1 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 5 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 22 August 2014.
All research outputs
#18,376,056
of 22,760,687 outputs
Outputs from Breast Cancer Research and Treatment
#3,712
of 4,652 outputs
Outputs of similar age
#167,990
of 235,583 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#43
of 59 outputs
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