PMID- 19588500
OWN - NLM
STAT- MEDLINE
DCOM- 20100113
LR  - 20220321
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 126
IP  - 2
DP  - 2010 Jan 15
TI  - Biological effects induced by insulin-like growth factor binding protein 3 
      (IGFBP-3) in malignant melanoma.
PG  - 350-61
LID - 10.1002/ijc.24727 [doi]
AB  - The insulin like growth factor (IGF) signaling pathway has been shown to 
      contribute to melanoma progression, but little is known about the role of the IGF 
      binding protein 3 (IGFBP-3) in melanoma biology. The aim of the present study was 
      to characterize expression, function and regulation of IGFBP-3 in malignant 
      melanomas and study its potential as a biomarker. The expression of IGFBP-3 
      varied between different human melanoma cell lines and reintroduction of the 
      protein in non-expressing cells led to induction of apoptosis. Interestingly, in 
      cell lines expressing endogenous IGFBP-3, siRNA silencing of the protein led to a 
      cell line-dependent decrease in proliferation, but had no effect on apoptosis and 
      invasion. Examination of patient material showed that IGFBP-3 is unexpressed in 
      benign nevi while a slight increase in protein expression was seen in primary and 
      metastatic melanoma. However, expression of the protein was low and no 
      correlation was found with circulating levels of IGFBP-3 in serum, suggesting 
      that IGFBP-3 has limited potential as a predictive marker in malignant melanoma. 
      We showed that promoter methylation of IGFBP-3 occurred in both melanoma cell 
      lines and patient material, implicating epigenetic silencing as a regulation 
      mechanism. Furthermore, expression of the protein was shown to be regulated by 
      the PI3-kinase/AKT and MAPK/ERK1/2 pathways. In summary, our findings suggest 
      that IGFBP-3 can exert dual functional effects influencing both apoptosis and 
      proliferation. Development of resistance to the antiproliferative effects of 
      IGFBP-3 may be an important step in progression of malignant melanomas.
FAU - Oy, Geir Frode
AU  - Oy GF
AD  - Department of Tumor Biology, Institute for Cancer Research, Oslo, Norway.
FAU - Slipicevic, Ana
AU  - Slipicevic A
FAU - Davidson, Ben
AU  - Davidson B
FAU - Solberg Faye, Ragnar
AU  - Solberg Faye R
FAU - Maelandsmo, Gunhild M
AU  - Maelandsmo GM
FAU - Florenes, Vivi Ann
AU  - Florenes VA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - DNA Methylation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Insulin-Like Growth Factor Binding Protein 3/*genetics/metabolism
MH  - Melanoma/*genetics/metabolism/pathology
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
EDAT- 2009/07/10 09:00
MHDA- 2010/01/14 06:00
CRDT- 2009/07/10 09:00
PHST- 2009/07/10 09:00 [entrez]
PHST- 2009/07/10 09:00 [pubmed]
PHST- 2010/01/14 06:00 [medline]
AID - 10.1002/ijc.24727 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Jan 15;126(2):350-61. doi: 10.1002/ijc.24727.