PMID- 18755809
OWN - NLM
STAT- MEDLINE
DCOM- 20081126
LR  - 20211020
IS  - 0193-1857 (Print)
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 295
IP  - 4
DP  - 2008 Oct
TI  - Somatostatin stimulates menin gene expression by inhibiting protein kinase A.
PG  - G843-54
LID - 10.1152/ajpgi.00607.2007 [doi]
AB  - Somatostatin is a potent inhibitor of gastrin secretion and gene expression. 
      Menin is a 67-kDa protein product of the multiple endocrine neoplasia type 1 
      (MEN1) gene that when mutated leads to duodenal gastrinomas, a tumor that 
      overproduces the hormone gastrin. These observations suggest that menin might 
      normally inhibit gastrin gene expression in its role as a tumor suppressor. Since 
      somatostatin and ostensibly menin are both inhibitors of gastrin, we hypothesized 
      that somatostatin signaling directly induces menin. Menin protein expression was 
      significantly lower in somatostatin-null mice, which are hypergastrinemic. We 
      found by immunohistochemistry that somatostatin receptor-positive cells (SSTR2A) 
      express menin. Mice were treated with the somatostatin analog octreotide to 
      determine whether activation of somatostatin signaling induced menin. We found 
      that octreotide increased the number of menin-expressing cells, menin mRNA, and 
      menin protein expression. Moreover, the induction by octreotide was greater in 
      the duodenum than in the antrum. The increase in menin observed in vivo was 
      recapitulated by treating AGS and STC cell lines with octreotide, demonstrating 
      that the regulation was direct. The induction required suppression of protein 
      kinase A (PKA) since forskolin treatment suppressed menin protein levels and 
      octreotide inhibited PKA enzyme activity. Small-interfering RNA-mediated 
      suppression of PKA levels raised basal levels of menin protein and prevented 
      further induction by octreotide. Using AGS cells, we also showed for the first 
      time that menin directly inhibits endogenous gastrin gene expression. In 
      conclusion, somatostatin receptor activation induces menin expression by 
      suppressing PKA activation.
FAU - Mensah-Osman, Edith
AU  - Mensah-Osman E
AD  - Department of Internal Medicine, Division of Gastroenterology, University of 
      Michigan, Ann Arbor, Michigan, USA.
FAU - Zavros, Yana
AU  - Zavros Y
FAU - Merchant, Juanita L
AU  - Merchant JL
LA  - eng
GR  - R37 DK045729/DK/NIDDK NIH HHS/United States
GR  - R37 DK045729-15/DK/NIDDK NIH HHS/United States
GR  - R01-DK45729/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080828
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Gastrins)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Somatostatin)
RN  - 51110-01-1 (Somatostatin)
RN  - D73QL0OMU2 (somatostatin receptor 2)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - Animals
MH  - Cyclic AMP-Dependent Protein Kinases/*antagonists & inhibitors
MH  - Duodenum/metabolism
MH  - Gastrins/genetics/metabolism
MH  - Gene Expression/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Octreotide/pharmacology
MH  - Proto-Oncogene Proteins/biosynthesis/*genetics
MH  - Pyloric Antrum/metabolism
MH  - Receptors, Somatostatin/physiology
MH  - Somatostatin/*pharmacology
PMC - PMC2575917
EDAT- 2008/08/30 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/10/01
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
PHST- 2009/10/01 00:00 [pmc-release]
AID - 00607.2007 [pii]
AID - G-00607-2007 [pii]
AID - 10.1152/ajpgi.00607.2007 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G843-54. doi: 
      10.1152/ajpgi.00607.2007. Epub 2008 Aug 28.