PMID- 9745428
OWN - NLM
STAT- MEDLINE
DCOM- 19981008
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 83
IP  - 9
DP  - 1998 Sep
TI  - The MEN-1 gene is rarely down-regulated in pituitary adenomas.
PG  - 3210-2
AB  - The gene for multiple endocrine neoplasia type 1 (MEN-1) has recently been cloned 
      and encodes a putative tumor suppressor protein named menin. We have previously 
      reported inactivating MEN-1 gene mutations associated with loss of heterozygosity 
      (LOH) of the normal allele in tumors of patients with MEN-1 and in some sporadic 
      pituitary tumors. These genetic alterations, however, are noted in no more than 
      10% of sporadic adenomas. To investigate whether other mechanisms may result in 
      down-regulation of menin gene expression in pituitary adenomas, we examined menin 
      gene expression by semiquantitative RT-PCR in 60 sporadic pituitary adenomas. 
      Ribonucleic acid (RNA) was extracted from surgically resected, morphologically 
      characterized tumors. Primers were designed to amplify a 257-bp fragment spanning 
      exons 4-6 of the MEN-1 gene. A product of the predicted size was amplified from 
      normal pituitary samples as well as from adenomas. Competitive PCR was performed 
      with the housekeeping gene PGK-1 to quantitate menin gene expression. A 
      comparable ratio of menin/PGK-1 messenger RNA was identified in all but three 
      samples; in two tumors with LOH, menin expression was weak, and in one tumor, 
      menin messenger RNA was undetectable, associated with LOH and mutation of the 
      other allele. Reduced expression of menin in some sporadic adenomas is consistent 
      with a putative tumor suppressor role for this gene product. However, lack of 
      menin down-regulation in the majority of these tumors, which exhibit LOH at 11q13 
      in up to 20% of cases, provides compelling evidence for an additional tumor 
      suppressor gene at this locus, which is more commonly involved in the 
      pathogenesis of pituitary neoplasms.
FAU - Asa, S L
AU  - Asa SL
AD  - Department of Pathology, Mount Sinai Hospital, University of Toronto, Ontario, 
      Canada. sasa@mtsinai.on.ca
FAU - Somers, K
AU  - Somers K
FAU - Ezzat, S
AU  - Ezzat S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
SB  - IM
MH  - Adenoma/*genetics
MH  - Adult
MH  - Aged
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Gene Expression
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Pituitary Neoplasms/*genetics
MH  - Polymerase Chain Reaction
MH  - *Proto-Oncogene Proteins
MH  - RNA, Messenger/analysis
MH  - RNA-Directed DNA Polymerase
EDAT- 1998/09/24 00:00
MHDA- 1998/09/24 00:01
CRDT- 1998/09/24 00:00
PHST- 1998/09/24 00:00 [pubmed]
PHST- 1998/09/24 00:01 [medline]
PHST- 1998/09/24 00:00 [entrez]
AID - 10.1210/jcem.83.9.5138 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1998 Sep;83(9):3210-2. doi: 10.1210/jcem.83.9.5138.