PMID- 28247944 OWN - NLM STAT- MEDLINE DCOM- 20170911 LR - 20220318 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) 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: 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 PMCR- 2017/05/01 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] PHST- 2017/05/01 00:00 [pmc-release] AID - CAS13214 [pii] 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.