PMID- 25284587
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20240210
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 34
IP  - 29
DP  - 2015 Jul
TI  - Genomic interaction between ER and HMGB2 identifies DDX18 as a novel driver of 
      endocrine resistance in breast cancer cells.
PG  - 3871-80
LID - 10.1038/onc.2014.323 [doi]
AB  - Breast cancer resistance to endocrine therapies such as tamoxifen and aromatase 
      inhibitors is a significant clinical problem. Steroid receptor coactivator-1 
      (SRC-1), a coregulatory protein of the oestrogen receptor (ER), has previously 
      been shown to have a significant role in the progression of breast cancer. The 
      chromatin protein high mobility group box 2 (HMGB2) was identified as an SRC-1 
      interacting protein in the endocrine-resistant setting. We investigated the 
      expression of HMGB2 in a cohort of 1068 breast cancer patients and found an 
      association with increased disease-free survival time in patients treated with 
      endocrine therapy. However, it was also verified that HMGB2 expression could be 
      switched on in endocrine-resistant tumours from breast cancer patients. To 
      explore the function of this poorly characterized protein, we performed HMGB2 
      ChIPseq and found distinct binding patterns between the two contexts. In the 
      resistant setting, the HMGB2, SRC-1 and ER complex are enriched at promoter 
      regions of target genes, with bioinformatic analysis indicating a switch in 
      binding partners between the sensitive and resistant phenotypes. Integration of 
      binding and gene expression data reveals a concise set of target genes of this 
      complex including the RNA helicase DDX18. Modulation of DDX18 directly affects 
      growth of tamoxifen-resistant cells, suggesting that it may be a critical 
      downstream effector of the HMGB2:ER complex. This study defines HMGB2 
      interactions with the ER complex at specific target genes in the 
      tamoxifen-resistant setting.
FAU - Redmond, A M
AU  - Redmond AM
AD  - 1] Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland [2] Cancer Research UK, Cambridge Institute, 
      University of Cambridge, Cambridge, UK.
FAU - Byrne, C
AU  - Byrne C
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
FAU - Bane, F T
AU  - Bane FT
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
FAU - Brown, G D
AU  - Brown GD
AD  - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.
FAU - Tibbitts, P
AU  - Tibbitts P
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
FAU - O'Brien, K
AU  - O'Brien K
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
FAU - Hill, A D K
AU  - Hill AD
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
FAU - Carroll, J S
AU  - Carroll JS
AD  - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.
FAU - Young, L S
AU  - Young LS
AD  - Endocrine Oncology Research Group, Department of Surgery, Royal College of 
      Surgeons in Ireland, Dublin, Ireland.
LA  - eng
GR  - 20411/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141006
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (HMGB2 Protein)
RN  - 0 (Receptors, Estrogen)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 3.6.1.- (DDX18 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Hormonal/pharmacology/therapeutic use
MH  - Breast Neoplasms/drug therapy/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - DEAD-box RNA Helicases/genetics/*metabolism
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - HMGB2 Protein/genetics/*metabolism
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - MCF-7 Cells
MH  - Mice, Inbred BALB C
MH  - Mice, SCID
MH  - Nuclear Receptor Coactivator 1/genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - Receptors, Estrogen/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tamoxifen/pharmacology/therapeutic use
MH  - Xenograft Model Antitumor Assays
EDAT- 2014/10/07 06:00
MHDA- 2015/10/17 06:00
CRDT- 2014/10/07 06:00
PHST- 2014/02/12 00:00 [received]
PHST- 2014/08/04 00:00 [revised]
PHST- 2014/08/24 00:00 [accepted]
PHST- 2014/10/07 06:00 [entrez]
PHST- 2014/10/07 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
AID - onc2014323 [pii]
AID - 10.1038/onc.2014.323 [doi]
PST - ppublish
SO  - Oncogene. 2015 Jul;34(29):3871-80. doi: 10.1038/onc.2014.323. Epub 2014 Oct 6.