PMID- 17664862
OWN - NLM
STAT- MEDLINE
DCOM- 20071023
LR  - 20120625
IS  - 1423-0194 (Electronic)
IS  - 0028-3835 (Linking)
VI  - 86
IP  - 2
DP  - 2007
TI  - Cyclin-dependent kinase 4 (CDK4) expression in pancreatic endocrine tumors.
PG  - 112-8
AB  - BACKGROUND/AIMS: Pancreatic endocrine tumors (PETs) occur sporadically, in 
      association with the multiple endocrine neoplasia type 1 (MEN1) and the von 
      Hippel-Lindau syndromes. CDK4 is central to the cell cycle control in pancreatic 
      beta cells, and we have assessed whether CDK4 expression is deregulated in 18 
      human sporadic or familial PETs. METHODS: Real-time quantitative PCR, 
      immunohistochemistry, DNA sequencing, and Western blot analysis were used. 
      RESULTS: CDK4 mRNA was expressed in all PETs within the range of the arbitrary 
      control. CDK4 protein was absent in normal pancreatic islets but distinctly 
      expressed in all PETs as determined by immunohistochemistry. CDK4 expression was 
      confirmed by Western blot analysis. No significant differences of CDK4 expression 
      were observed between the groups of benign and malignant PETs or between tumors 
      with or without MEN1 gene mutations. CDK4 expression was not due to gene 
      amplification, and no mutations were identified in coding exons and RNA splice 
      sites. c-Myc is known to be overexpressed in PETs and directly augments CDK4 
      expression in other cell types. Analysis of consecutive tissue sections for CDK4 
      and c-Myc showed overlapping homo- or heterogeneous immunostaining in all 18 
      PETs. CONCLUSION: We conclude that CDK4 and c-Myc is generally expressed in 
      benign and malignant PETs, and regardless of MEN1 mutational status. Targeting of 
      CDK4 may present an alternative to traditional chemotherapy of PETs in the 
      future.
CI  - (c) 2007 S. Karger AG, Basel.
FAU - Lindberg, Daniel
AU  - Lindberg D
AD  - Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, 
      Uppsala, Sweden.
FAU - Hessman, Ola
AU  - Hessman O
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 - 20070730
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
SB  - IM
MH  - Cyclin-Dependent Kinase 4/*genetics/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Islets of Langerhans/pathology
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism/pathology
MH  - Mutation
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology
MH  - Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - von Hippel-Lindau Disease/genetics/metabolism/pathology
EDAT- 2007/08/01 09:00
MHDA- 2007/10/24 09:00
CRDT- 2007/08/01 09:00
PHST- 2007/03/01 00:00 [received]
PHST- 2007/06/26 00:00 [accepted]
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2007/10/24 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
AID - 000106762 [pii]
AID - 10.1159/000106762 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2007;86(2):112-8. doi: 10.1159/000106762. Epub 2007 Jul 30.