PMID- 11733227
OWN - NLM
STAT- MEDLINE
DCOM- 20020304
LR  - 20211203
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 8
IP  - 4
DP  - 2001 Dec
TI  - Oncogenic co-operation in beta-cell tumorigenesis.
PG  - 307-14
AB  - Pancreatic islet neoplasms are rare endocrine tumours. The most common type is of 
      beta-cell origin and is known as insulinoma, which can be either benign or 
      malignant. The majority of insulinomas arise sporadically, but a small proportion 
      develop as part of the hereditary multiple endocrine neoplasia type 1 (MEN1) 
      syndrome. As for many human tumours, the genetic events that occur during the 
      initiation and progression of insulinoma are poorly known. The men1 gene product, 
      menin, is deficient in most hereditary cases, but is not obviously affected in 
      the majority of sporadic tumours. Activation of the proto-oncogenes c-myc and ras 
      has been observed during malignant progression, but their role in tumour 
      initiation remains unproven. To address these questions, transgenic mouse models 
      have been increasingly used to explore molecular and genetic events that might 
      also precipitate human neoplasia. Transgenic mice expressing SV40 large T-antigen 
      (Tag) oncogene in beta-cells develop tumours in a multi-stage progression from 
      hyperplasia, angiogenesis, to solid encapsulated tumours. However, Tag, which 
      inactivates the key tumour suppressors p53 and Rb, is not known to be involved in 
      the pathogenesis of human insulinoma. The proto-oncogene, c-myc is implicated in 
      beta-cell growth in both diabetes and tumorigenesis. Activation of Myc appears to 
      be an early event in progression of human insulinoma. The effect of deregulated 
      Myc expression on adult beta-cells in vivo has recently been investigated by 
      developing transgenic mouse models in which the activity of Myc can be regulated 
      ectopically. Although Myc activation initially promotes both proliferation and 
      apoptosis in pancreatic beta-cells, apoptosis is the predominant outcome, giving 
      rise to islet involution and diabetes. Importantly, inhibiting Myc-induced 
      apoptosis (by co-expression of Bcl-x(L)) leads to significantly enlarged islets, 
      many becoming highly vascularized, hyperplastic and invasive. These results 
      suggest that, in the pancreatic beta-cells, early suppression of apoptosis is 
      essential for the survival of Myc-activated beta-cells and islet neoplasia.
FAU - Pelengaris, S
AU  - Pelengaris S
AD  - Molecular Medicine Research Centre, Department of Biological Sciences, University 
      of Warwick, Coventry CV4 7AL, UK. spelengaris@bio.warwick.ac.uk
FAU - Khan, M
AU  - Khan M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins c-myc)
SB  - IM
MH  - Adenoma, Islet Cell/genetics/pathology
MH  - Adult
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/genetics/physiology
MH  - Apoptosis/genetics
MH  - Cell Division/genetics
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cell Transformation, Viral/genetics
MH  - Child
MH  - Disease Progression
MH  - Genes, myc
MH  - Genes, ras
MH  - Humans
MH  - Insulinoma/*genetics/pathology
MH  - Islets of Langerhans/metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Multiple Endocrine Neoplasia Type 1/genetics
MH  - *Oncogenes
MH  - Pancreatic Neoplasms/*genetics
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-myc/physiology
MH  - Proto-Oncogenes
MH  - Simian virus 40/genetics/physiology
RF  - 38
EDAT- 2001/12/06 10:00
MHDA- 2002/03/05 10:01
CRDT- 2001/12/06 10:00
PHST- 2001/12/06 10:00 [pubmed]
PHST- 2002/03/05 10:01 [medline]
PHST- 2001/12/06 10:00 [entrez]
AID - 10.1677/erc.0.0080307 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2001 Dec;8(4):307-14. doi: 10.1677/erc.0.0080307.