PMID- 28247944
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20210109
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 108
IP  - 5
DP  - 2017 May
TI  - Ets1 and ESE1 reciprocally regulate expression of ZEB1/ZEB2, dependent on ERK1/2 
      activity, in breast cancer cells.
PG  - 952-960
LID - 10.1111/cas.13214 [doi]
AB  - The epithelial-mesenchymal transition (EMT) is a crucial morphological event that
      occurs during progression of epithelial tumors. We reported previously that
      levels of the delta-crystallin/E2-box factor 1 (deltaEF1) family proteins (Zinc
      finger E-box binding homeobox 1 [ZEB1]/deltaEF1 and ZEB2/ Smad-interacting
      protein 1), key regulators of the EMT, are positively correlated with EMT
      phenotypes and aggressiveness of breast cancer. Here, we show that Ets1 induces
      ZEB expression and activates the ZEB1 promoter, independently of its threonine 38
      phosphorylation status. In the basal-like subtype of breast cancer cells, siRNAs 
      targeting Ets1 repressed expression of ZEBs and partially restored their
      epithelial phenotypes and sensitivity to antitumor drugs. Epithelium-specific ETS
      transcription factor 1 (ESE1), a member of the Ets transcription factor family,
      was originally characterized as being expressed in an epithelial-restricted
      pattern, placing it within the epithelium-specific ETS subfamily. ESE1, highly
      expressed in the luminal subtype of breast cancer cells, was repressed by
      activation of the MEK-ERK pathway, resulting in induction of ZEBs through Ets1
      upregulation. Conversely, Ets1, highly expressed in the basal-like subtype, was
      repressed by inactivation of MEK-ERK pathway, resulting in reduction of ZEBs
      through ESE1 upregulation. These findings suggest that ESE1 and Ets1, whose
      expressions are reciprocally regulated by the MEK-ERK pathway, define the EMT
      phenotype through controlling expression of ZEBs in each subtype of breast cancer
      cells.
CI  - (c) 2017 The Authors. Cancer Science published by John Wiley & Sons Australia,
      Ltd on behalf of Japanese Cancer Association.
FAU - Sinh, Nguyen Duy
AU  - Sinh ND
AD  - Department of Biochemistry, Interdisciplinary Graduate School of Medicine,
      University of Yamanashi, Chuo, Japan.
FAU - Endo, Kaori
AU  - Endo K
AD  - Department of Biochemistry, Interdisciplinary Graduate School of Medicine,
      University of Yamanashi, Chuo, Japan.
FAU - Miyazawa, Keiji
AU  - Miyazawa K
AD  - Department of Biochemistry, Interdisciplinary Graduate School of Medicine,
      University of Yamanashi, Chuo, Japan.
FAU - Saitoh, Masao
AU  - Saitoh M
AUID- ORCID: http://orcid.org/0000-0003-0793-1679
AD  - Department of Biochemistry, Interdisciplinary Graduate School of Medicine,
      University of Yamanashi, Chuo, Japan.
AD  - Center for Medical Education and Sciences, Interdisciplinary Graduate School of
      Medicine, University of Yamanashi, Chuo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170522
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ELF3 protein, human)
RN  - 0 (ETS1 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Proto-Oncogene Protein c-ets-1)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ZEB1 protein, human)
RN  - 0 (ZEB2 protein, human)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
RN  - 0 (Zinc Finger E-box-Binding Homeobox 1)
SB  - IM
MH  - Breast Neoplasms/*genetics
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/*genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Female
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - MAP Kinase Signaling System/*genetics
MH  - Phosphorylation/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Protein c-ets-1/*genetics
MH  - Proto-Oncogene Proteins c-ets/*genetics
MH  - RNA, Small Interfering/genetics
MH  - Repressor Proteins/*genetics
MH  - Signal Transduction/genetics
MH  - Transcription Factors/*genetics
MH  - Up-Regulation/genetics
MH  - Zinc Finger E-box Binding Homeobox 2
MH  - Zinc Finger E-box-Binding Homeobox 1/*genetics
PMC - PMC5448599
OTO - NOTNLM
OT  - EMT
OT  - ZEB
OT  - ESE1
OT  - Ets1
OT  - signal transduction
EDAT- 2017/03/02 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/03/02 06:00
PHST- 2016/12/26 00:00 [received]
PHST- 2017/02/21 00:00 [revised]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/03/02 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2017/03/02 06:00 [entrez]
AID - 10.1111/cas.13214 [doi]
PST - ppublish
SO  - Cancer Sci. 2017 May;108(5):952-960. doi: 10.1111/cas.13214. Epub 2017 May 22.