PMID- 16470538
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20091119
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 208
IP  - 5
DP  - 2006 Apr
TI  - PDGFRalpha, PDGFRbeta and KIT expression/activation in conventional 
      chondrosarcoma.
PG  - 615-23
AB  - Chondrosarcomas represent 20% of all primary bone sarcomas, and many studies have 
      attempted to unravel molecular targets for future development of new therapies. 
      The aim of this study was to investigate the expression/activation of PDGFRalpha, 
      PDGFRbeta and KIT receptor tyrosine kinases (RTKs) as potential therapeutic 
      targets in conventional central primary chondrosarcomas (CCS). The expression of 
      PDGFRalpha, PDGFRbeta and KIT RTKs was detected in 16 CCSs using 
      immunohistochemistry (IHC), and their level of expression and activation status 
      were analysed by immunoprecipitation and western blot experiments. PDGFRalpha, 
      PDGFRbeta and KIT cDNAs were screened to verify the presence of activating 
      mutations and the presence of the cognate ligands was analysed by means of 
      RT-PCR. RTK gene amplification was further studied by means of fluorescence in 
      situ hybridization (FISH) analysis. The immunophenotyping and biochemical 
      analyses showed that the CCSs co-expressed PDGFRalpha and PDGFRbeta, with the 
      latter showing definitively greater protein expression and phosphorylation 
      levels. PDGFRbeta was expressed but not activated in control healthy joint 
      cartilage, in line with no PDGFB detection. Conversely, the KIT gene product did 
      not seem to play a relevant role. These findings, in the absence of activating 
      mutations or an abnormal genomic profile and the presence of PDGFA and PDGFB 
      expression, are consistent with an autocrine/paracrine loop activation of the 
      corresponding receptors. The CCS gene profile described here offers a rationale 
      for the use of RTK inhibitors alone or in combination with chemotherapy, and 
      supports further investigation of RTKs and their downstream signals.
FAU - Lagonigro, M S
AU  - Lagonigro MS
AD  - Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei 
      Tumori, Milan, Italy.
FAU - Tamborini, E
AU  - Tamborini E
FAU - Negri, T
AU  - Negri T
FAU - Staurengo, S
AU  - Staurengo S
FAU - Dagrada, G P
AU  - Dagrada GP
FAU - Miselli, F
AU  - Miselli F
FAU - Gabanti, E
AU  - Gabanti E
FAU - Greco, A
AU  - Greco A
FAU - Casali, P G
AU  - Casali PG
FAU - Carbone, A
AU  - Carbone A
FAU - Pierotti, M A
AU  - Pierotti MA
FAU - Pilotti, S
AU  - Pilotti S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Ligands)
RN  - 0 (Neoplasm Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Bone Neoplasms/genetics/*metabolism
MH  - Chondrosarcoma/genetics/*metabolism
MH  - Gene Expression Profiling/methods
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Ligands
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-kit/genetics/metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics/metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
EDAT- 2006/02/14 09:00
MHDA- 2006/05/04 09:00
CRDT- 2006/02/14 09:00
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
AID - 10.1002/path.1945 [doi]
PST - ppublish
SO  - J Pathol. 2006 Apr;208(5):615-23. doi: 10.1002/path.1945.