PMID- 20706287
OWN - NLM
STAT- MEDLINE
DCOM- 20110127
LR  - 20101018
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 17
IP  - 11
DP  - 2010 Nov
TI  - Ribozyme-mediated compensatory induction of menin-oncosuppressor function in 
      primary fibroblasts from MEN1 patients.
PG  - 814-25
LID - 10.1038/cgt.2010.39 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by the 
      occurrence of tumors of parathyroids, neuroendocrine cells of the 
      gastro-enteropancreatic tract and anterior pituitary. MEN1 gene encodes 
      menin-oncosuppressor protein. Loss of heterozygosity at 11q13 is typical of MEN1 
      tumors. We have analyzed the MEN1 mRNA and menin expression in fibroblasts from 
      normal skin biopsies and from MEN1 patients (two with a frameshift 738del4 (exon 
      3) mutation, introducing a premature stop codon, and an individual with an R460X 
      (exon 10) nonsense mutation). The expression of full-length menin protein did not 
      differ between MEN1 and normal fibroblasts. Wild-type alleles mRNAs were 
      expressed in MEN1 patients, whereas mutant alleles were partially degraded by 
      nonsense-mediated mRNA decay pathway, suggesting a mechanism of compensation for 
      allelic loss by the up-regulation of wild-type menin expression at a 
      post-transcriptional level. Small-interfering RNA silencing of the wild-type mRNA 
      allele abolished menin compensation, whereas the ribozyme silencing of the 
      MEN1-mutated mRNA allele resulted in strongly enhanced wild-type menin 
      expression. Gel-retardation analysis showed that in vitro-specific RNA-protein 
      complexes bound to MEN1 mRNA. These findings contribute to the understanding of 
      tumorigenesis in MEN1, offering the basis for the development of RNA-based 
      therapies in MEN1 gene mutation carriers.
FAU - Luzi, E
AU  - Luzi E
AD  - Department of Internal Medicine, Metabolic Bone Unit, Regional Center for 
      Hereditary Endocrine Tumors, Azienda Ospedaliera Universitaria Careggi, Florence, 
      Italy.
FAU - Marini, F
AU  - Marini F
FAU - Tognarini, I
AU  - Tognarini I
FAU - Carbonell Sala, S
AU  - Carbonell Sala S
FAU - Galli, G
AU  - Galli G
FAU - Falchetti, A
AU  - Falchetti A
FAU - Brandi, M L
AU  - Brandi ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100813
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Catalytic)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Adult
MH  - Caspase 8/metabolism
MH  - Exons
MH  - Female
MH  - Fibroblasts/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*metabolism
MH  - Mutation
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - RNA Interference
MH  - RNA, Catalytic/*metabolism
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/*metabolism
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2010/08/14 06:00
MHDA- 2011/01/29 06:00
CRDT- 2010/08/14 06:00
PHST- 2010/08/14 06:00 [entrez]
PHST- 2010/08/14 06:00 [pubmed]
PHST- 2011/01/29 06:00 [medline]
AID - cgt201039 [pii]
AID - 10.1038/cgt.2010.39 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2010 Nov;17(11):814-25. doi: 10.1038/cgt.2010.39. Epub 2010 Aug 
      13.