PMID- 17803708
OWN - NLM
STAT- MEDLINE
DCOM- 20120424
LR  - 20080117
IS  - 1365-2265 (Electronic)
IS  - 0300-0664 (Linking)
VI  - 68
IP  - 2
DP  - 2008 Feb
TI  - Evaluation of CDKN2C/p18, CDKN1B/p27 and CDKN2B/p15 mRNA expression, and CpG 
      methylation status in sporadic and MEN1-associated pancreatic endocrine tumours.
PG  - 271-7
AB  - OBJECTIVE: Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene 
      at 11q13, enhances transcription of the cyclin-dependent kinase inhibitors 
      (CDIs), CDKN2C (p18) and CDKN1B (p27) in mouse pancreatic islets, and 
      inactivation of menin reduced CDKN2B (p15) expression in this mouse model. Here, 
      we have compared the relative mRNA expression level and CpG methylation status of 
      p18, p27 and p15 in 18 pancreatic endocrine tumours (PETs) with or without MEN1 
      gene mutations. DESIGN: Real-time quantitative PCR, DNA sequencing and 
      pyrosequencing methylation analysis were employed. RESULTS: The p18 gene was 
      expressed in 15 out of the 18 analysed PETs. The expression level was within the 
      range of the normal pancreatic tissues or higher. Of the three remaining tumours 
      with no expression, two displayed loss of heterozygocity (LOH) at 11q13, one 
      derived from a MEN1 patient. The p27 gene was expressed in all PETs at a level 
      higher than the normal pancreatic tissues, except for one tumour. Promoter 
      methylation was not detected for p18 and p27. p15 expression was undetectable in 
      8/18 (44%) of the PETs, and no general relations to tumour syndrome, malignancy 
      or MEN1 gene mutations were evident. This was not due to homozygous gene 
      deletions, but the p15 promoter was hypermethylated in two insulinomas. No 
      mutations were found in the p15 gene. CONCLUSIONS: Expression of p15, p18 and p27 
      was not generally related to the MEN1 gene mutational status of the investigated 
      18 PETs. The p15 gene was silenced by promoter hypermethylation in two tumours. 
      Dysregulation of menin and the CDIs are important in PET tumorigenesis, and their 
      interrelations remain to be elucidated.
FAU - Lindberg, Daniel
AU  - Lindberg D
AD  - Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, 
      Uppsala, Sweden.
FAU - Akerstrom, Goran
AU  - Akerstrom G
FAU - Westin, Gunnar
AU  - Westin G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070904
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (CDKN1B protein, human)
RN  - 0 (CDKN2B protein, human)
RN  - 0 (CDKN2C protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p15)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Cyclin-Dependent Kinase Inhibitor p15/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p18/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - DNA Methylation/genetics
MH  - Humans
MH  - Mutation
MH  - Pancreatic Neoplasms/*genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
EDAT- 2007/09/07 09:00
MHDA- 2012/04/25 06:00
CRDT- 2007/09/07 09:00
PHST- 2007/09/07 09:00 [pubmed]
PHST- 2012/04/25 06:00 [medline]
PHST- 2007/09/07 09:00 [entrez]
AID - CEN3034 [pii]
AID - 10.1111/j.1365-2265.2007.03034.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2008 Feb;68(2):271-7. doi: 
      10.1111/j.1365-2265.2007.03034.x. Epub 2007 Sep 4.