PMID- 22037578
OWN - NLM
STAT- MEDLINE
DCOM- 20120118
LR  - 20191210
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 415
IP  - 2
DP  - 2011 Nov 18
TI  - Haploinsufficient and predominant expression of multiple endocrine neoplasia type 
      1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs.
PG  - 378-83
LID - 10.1016/j.bbrc.2011.10.077 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominantly 
      inherited syndrome characterized by parathyroid, gastro-entero-pancreatic and 
      anterior pituitary tumors. Although the tissue selectivity of tumors in specific 
      endocrine organs is the very essence of MEN1, the mechanisms underlying the 
      tissue-selectivity of tumors remain unknown. The product of the Men1 gene, menin, 
      and mixed lineage leukemia (MLL) have been found to cooperatively regulate 
      p27(Kip1)/CDKN1B (p27) and p18(Ink4C)/CDKN2C (p18) genes. However, there are no 
      reports on the tissue distribution of these MEN1-related genes. We investigated 
      the expression of these genes in the endocrine and non-endocrine organs of 
      wild-type, Men1 knockout and MLL knockout mice. Men1 mRNA was expressed at a 
      similar level in endocrine and non-endocrine organs. However, MLL, p27 and p18 
      mRNAs were predominantly expressed in the endocrine organs. Notably, p27 and MLL 
      mRNAs were expressed in the pituitary gland at levels approximately 12- and 
      17-fold higher than those in the liver. The heterozygotes of Men1 knockout mice 
      the levels of MLL, p27 and p18 mRNAs did not differ from those in the wild-type 
      mice. In contrast, heterozygotes of MLL knockout mice showed significant 
      reductions in p27 mRNA as well as protein levels in the pituitary and p27 and p18 
      in the pancreatic islets, but not in the liver. This study demonstrated for the 
      first time the predominant expression MEN1-related genes, particularly MLL and 
      p27, in the endocrine organs, and a tissue-specific haploinsuffiency of MLL, but 
      not menin, may lead to a decrease in levels of p27 and p18 mRNAs in endocrine 
      organs. These findings may provide basic information for understanding the 
      mechanisms of tissue selectivity of the tumorigenesis in patients with MEN1.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Taguchi, Ryo
AU  - Taguchi R
AD  - Department of Medicine and Molecular Science, Gunma University Graduate School of 
      Medicine, Maebashi, Gunma 371-8511, Japan.
FAU - Yamada, Masanobu
AU  - Yamada M
FAU - Horiguchi, Kazuhiko
AU  - Horiguchi K
FAU - Tomaru, Takuya
AU  - Tomaru T
FAU - Ozawa, Atsushi
AU  - Ozawa A
FAU - Shibusawa, Nobuyuki
AU  - Shibusawa N
FAU - Hashimoto, Koshi
AU  - Hashimoto K
FAU - Okada, Shuichi
AU  - Okada S
FAU - Satoh, Tetsurou
AU  - Satoh T
FAU - Mori, Masatomo
AU  - Mori M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111021
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cdkn1b protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (Kmt2a protein, mouse)
SB  - IM
MH  - Adrenal Glands/metabolism
MH  - Animals
MH  - Cyclin-Dependent Kinase Inhibitor p18/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Haploinsufficiency
MH  - Histone-Lysine N-Methyltransferase
MH  - Islets of Langerhans/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics
MH  - Pituitary Gland/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Testis/metabolism
EDAT- 2011/11/01 06:00
MHDA- 2012/01/19 06:00
CRDT- 2011/11/01 06:00
PHST- 2011/10/01 00:00 [received]
PHST- 2011/10/13 00:00 [accepted]
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/01/19 06:00 [medline]
AID - S0006-291X(11)01889-4 [pii]
AID - 10.1016/j.bbrc.2011.10.077 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Nov 18;415(2):378-83. doi: 
      10.1016/j.bbrc.2011.10.077. Epub 2011 Oct 21.