PMID- 28188614
OWN - NLM
STAT- MEDLINE
DCOM- 20170509
LR  - 20220408
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 242
IP  - 1
DP  - 2017 May
TI  - Foxa2, a novel protein partner of the tumour suppressor menin, is deregulated in 
      mouse and human MEN1 glucagonomas.
PG  - 90-101
LID - 10.1002/path.4885 [doi]
AB  - Foxa2, known as one of the pioneer factors, plays a crucial role in islet 
      development and endocrine functions. Its expression and biological functions are 
      regulated by various factors, including, in particular, insulin and glucagon. 
      However, its expression and biological role in adult pancreatic alpha-cells remain 
      elusive. In the current study, we showed that Foxa2 was overexpressed in islets 
      from alpha-cell-specific Men1 mutant mice, at both the transcriptional level and the 
      protein level. More importantly, immunostaining analyses showed its prominent 
      nuclear accumulation, specifically in alpha-cells, at a very early stage after Men1 
      disruption. Similar nuclear FOXA2 expression was also detected in a substantial 
      proportion (12/19) of human multiple endocrine neoplasia type 1 (MEN1) 
      glucagonomas. Interestingly, our data revealed an interaction between Foxa2 and 
      menin encoded by the Men1 gene. Furthermore, using several approaches, we 
      demonstrated the relevance of this interaction in the regulation of two tested 
      Foxa2 target genes, including the autoregulation of the Foxa2 promoter by Foxa2 
      itself. The current study establishes menin, a novel protein partner of Foxa2, as 
      a regulator of Foxa2, the biological functions of which extend beyond the 
      pancreatic endocrine cells. Copyright (c) 2017 Pathological Society of Great 
      Britain and Ireland. Published by John Wiley & Sons, Ltd.
CI  - Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Bonnavion, Remy
AU  - Bonnavion R
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
FAU - Teinturier, Romain
AU  - Teinturier R
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
FAU - Gherardi, Samuele
AU  - Gherardi S
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
FAU - Leteurtre, Emmanuelle
AU  - Leteurtre E
AD  - Institut de Pathologie, CHRU de Lille, Lille, France.
AD  - Department of Endocrinology and Metabolism, Univ. Lille 2, INSERM UMR 1190, 
      Lille, France.
FAU - Yu, Run
AU  - Yu R
AD  - Division of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
FAU - Cordier-Bussat, Martine
AU  - Cordier-Bussat M
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
FAU - Du, Rui
AU  - Du R
AD  - The E-Institute of Shanghai, Sino-French Life Science and Genomic Centre, Ruijin 
      Hospital, Shanghai, PR China.
AD  - Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, 
      Shanghai Jiao-Tong University, Shanghai, PR China.
FAU - Pattou, Francois
AU  - Pattou F
AD  - Department of Endocrinology and Metabolism, Univ. Lille 2, INSERM UMR 1190, 
      Lille, France.
AD  - CHRU Lille, Endocrine Surgery, Lille, France.
FAU - Vantyghem, Marie-Christine
AU  - Vantyghem MC
AD  - Department of Endocrinology and Metabolism, Univ. Lille 2, INSERM UMR 1190, 
      Lille, France.
AD  - CHRU Lille, Endocrinology, Lille, France.
FAU - Bertolino, Philippe
AU  - Bertolino P
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
FAU - Lu, Jieli
AU  - Lu J
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
AD  - The E-Institute of Shanghai, Sino-French Life Science and Genomic Centre, Ruijin 
      Hospital, Shanghai, PR China.
AD  - Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, 
      Shanghai Jiao-Tong University, Shanghai, PR China.
FAU - Zhang, Chang Xian
AU  - Zhang CX
AUID- ORCID: 0000-0002-5443-8951
AD  - INSERM U1052, Lyon, France.
AD  - CNRS UMR5286, Lyon, France.
AD  - Universite de Lyon, Lyon, France.
AD  - The E-Institute of Shanghai, Sino-French Life Science and Genomic Centre, Ruijin 
      Hospital, Shanghai, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170327
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (FOXA2 protein, human)
RN  - 0 (Foxa2 protein, mouse)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 135845-92-0 (Hepatocyte Nuclear Factor 3-beta)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation, Neoplastic
MH  - Glucagonoma/genetics/*metabolism
MH  - Hepatocyte Nuclear Factor 3-beta/*biosynthesis/genetics
MH  - Humans
MH  - Mice, Transgenic
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*metabolism
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Foxa2
OT  - functional interaction
OT  - glucagonoma
OT  - menin
OT  - pancreatic alpha-cells
EDAT- 2017/02/12 06:00
MHDA- 2017/05/10 06:00
CRDT- 2017/02/12 06:00
PHST- 2015/09/11 00:00 [received]
PHST- 2017/01/17 00:00 [revised]
PHST- 2017/01/30 00:00 [accepted]
PHST- 2017/02/12 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2017/02/12 06:00 [entrez]
AID - 10.1002/path.4885 [doi]
PST - ppublish
SO  - J Pathol. 2017 May;242(1):90-101. doi: 10.1002/path.4885. Epub 2017 Mar 27.