PMID- 29973689
OWN - NLM
STAT- MEDLINE
DCOM- 20190228
LR  - 20210816
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 37
IP  - 44
DP  - 2018 Nov
TI  - GREB1 is an estrogen receptor-regulated tumour promoter that is frequently 
      expressed in ovarian cancer.
PG  - 5873-5886
LID - 10.1038/s41388-018-0377-y [doi]
AB  - Estrogenic hormone replacement therapy increases the risk of developing ovarian 
      cancer, and estrogen promotes tumour initiation and growth in mouse models of 
      this disease. GREB1 (Growth regulation by estrogen in breast cancer 1) is an ESR1 
      (estrogen receptor 1)-upregulated protein which may mediate estrogen action. 
      GREB1 knockdown prevents hormone-driven proliferation of several breast and 
      prostate cancer cell lines and prolongs survival of mice engrafted with ovarian 
      cancer cells, but its mechanism of action remains unclear. In this study, we 
      explored GREB1 function in ovarian cancer. GREB1 overexpression in ovarian cancer 
      cell lines increased cell proliferation and migration and promoted a mesenchymal 
      morphology associated with increased Col1a2, which encodes a collagen I subunit. 
      GREB1 knockdown inhibited proliferation and promoted an epithelial morphology 
      associated with decreased Col1a2. In human tissues, GREB1 was expressed in all 
      ESR1-expressing tissues throughout the normal female reproductive tract, in 
      addition to several tissues that did not show ESR1 expression. In a TMA of 
      ovarian cancer cases, GREB1 was expressed in 75-85% of serous, endometrioid, 
      mucinous, and clear cell carcinomas. Serous, endometrioid, and mucinous ovarian 
      cancers were almost always positive for either ESR1 or GREB1, suggesting a 
      possible reliance on signalling through ESR1 and/or GREB1. Targeting GREB1 may 
      inhibit tumour-promoting pathways both downstream and independent of ESR1 and is 
      therefore a possible treatment strategy worthy of further investigation.
FAU - Hodgkinson, Kendra
AU  - Hodgkinson K
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada.
AD  - Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, 
      Canada.
FAU - Forrest, Laura A
AU  - Forrest LA
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada.
AD  - Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, 
      Canada.
FAU - Vuong, Nhung
AU  - Vuong N
AUID- ORCID: 0000-0002-3437-6028
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada.
AD  - Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, 
      Canada.
FAU - Garson, Kenneth
AU  - Garson K
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada.
AD  - Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, 
      Canada.
FAU - Djordjevic, Bojana
AU  - Djordjevic B
AD  - Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University 
      of Ottawa, Ottawa, ON, Canada.
FAU - Vanderhyden, Barbara C
AU  - Vanderhyden BC
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada. bvanderhyden@ohri.ca.
AD  - Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, 
      Canada. bvanderhyden@ohri.ca.
LA  - eng
GR  - MOP-111194/Gouvernement du Canada | Canadian Institutes of Health Research 
      (Instituts de Recherche en Sante du Canada)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180704
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (COL1A2 protein, human)
RN  - 0 (Collagen Type I)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens)
RN  - 0 (GREB1 protein, human)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Collagen Type I/genetics/metabolism
MH  - Epithelial-Mesenchymal Transition
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Estrogens/genetics/physiology
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mice, SCID
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Ovarian Neoplasms/genetics/*metabolism
PMC - PMC6212416
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/07/06 06:00
MHDA- 2019/03/01 06:00
PMCR- 2018/07/04
CRDT- 2018/07/06 06:00
PHST- 2017/06/14 00:00 [received]
PHST- 2018/05/29 00:00 [accepted]
PHST- 2018/05/08 00:00 [revised]
PHST- 2018/07/06 06:00 [pubmed]
PHST- 2019/03/01 06:00 [medline]
PHST- 2018/07/06 06:00 [entrez]
PHST- 2018/07/04 00:00 [pmc-release]
AID - 10.1038/s41388-018-0377-y [pii]
AID - 377 [pii]
AID - 10.1038/s41388-018-0377-y [doi]
PST - ppublish
SO  - Oncogene. 2018 Nov;37(44):5873-5886. doi: 10.1038/s41388-018-0377-y. Epub 2018 
      Jul 4.