PMID- 23419452
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20211021
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 20
IP  - 1
DP  - 2013 Feb
TI  - The embryonic transcription factor Hlxb9 is a menin interacting partner that 
      controls pancreatic beta-cell proliferation and the expression of insulin 
      regulators.
PG  - 111-22
LID - 10.1530/ERC-12-0077 [doi]
AB  - The multiple endocrine neoplasia type 1 (MEN1) syndrome is caused by germline 
      mutations in the MEN1 gene encoding menin, with tissue-specific tumors of the 
      parathyroids, anterior pituitary, and enteropancreatic endocrine tissues. Also, 
      30-40% of sporadic pancreatic endocrine tumors show somatic MEN1 gene 
      inactivation. Although menin is expressed in all cell types of the pancreas, 
      mouse models with loss of menin in either pancreatic alpha-cells, or beta-cells, or 
      total pancreas develop beta-cell-specific endocrine tumors (insulinomas). Loss of 
      widely expressed tumor suppressor genes may produce tissue-specific tumors by 
      reactivating one or more embryonic-specific differentiation factors. Therefore, 
      we determined the effect of menin overexpression or knockdown on the expression 
      of beta-cell differentiation factors in a mouse beta-cell line (MIN6). We show that the 
      beta-cell differentiation factor Hlxb9 is posttranscriptionally upregulated upon 
      menin knockdown, and it interacts with menin. Hlxb9 reduces cell proliferation 
      and causes apoptosis in the presence of menin, and it regulates genes that 
      modulate insulin level. Thus, upon menin loss or from other causes, dysregulation 
      of Hlxb9 predicts a possible combined mechanism for beta-cell proliferation and 
      insulin production in insulinomas. These observations help to understand how a 
      ubiquitously expressed protein such as menin might control tissue-specific 
      tumorigenesis. Also, our findings identify Hlxb9 as an important factor for 
      beta-cell proliferation and insulin regulation.
FAU - Shi, Kerong
AU  - Shi K
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Parekh, Vaishali I
AU  - Parekh VI
FAU - Roy, Swarnava
AU  - Roy S
FAU - Desai, Shruti S
AU  - Desai SS
FAU - Agarwal, Sunita K
AU  - Agarwal SK
LA  - eng
GR  - ZIA DK075085-04/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20130218
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Insulin)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 140115-73-7 (Hb9 protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Blotting, Western
MH  - *Cell Differentiation
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Fibroblasts/cytology/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunoprecipitation
MH  - Insulin/genetics/*metabolism
MH  - Insulin-Secreting Cells/metabolism/*pathology
MH  - Insulinoma/genetics/metabolism/*pathology
MH  - Kidney/cytology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*physiology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/genetics/*metabolism
MH  - Two-Hybrid System Techniques
PMC - PMC6250975
MID - NIHMS996859
COIS- Declaration on interest The authors declare that there is no conflict of interest 
      that could be perceived as prejudicing the impartiality of the research reported.
EDAT- 2013/02/20 06:00
MHDA- 2013/07/03 06:00
PMCR- 2018/11/23
CRDT- 2013/02/20 06:00
PHST- 2013/02/20 06:00 [entrez]
PHST- 2013/02/20 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2018/11/23 00:00 [pmc-release]
AID - 20/1/111 [pii]
AID - 10.1530/ERC-12-0077 [doi]
PST - epublish
SO  - Endocr Relat Cancer. 2013 Feb 18;20(1):111-22. doi: 10.1530/ERC-12-0077. Print 
      2013 Feb.