PMID- 17143529
OWN - NLM
STAT- MEDLINE
DCOM- 20070131
LR  - 20211203
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 30
IP  - 1
DP  - 2007 Jan
TI  - Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the 
      invasive capability of prostate cancer cells in vitro.
PG  - 193-200
AB  - In the prostate, cellular growth and differentiation are finely regulated by a 
      complex interaction between stromal and epithelial cells under the control of 
      both autocrine and paracrine regulatory factors such as the nerve growth factor 
      (NGF). However, the role of NGF and its receptors including the high-affinity 
      p-140 TrkA and the low-affinity p75 NTR receptors remains controversial. Moreover 
      prostate tissues stored other neutrophins such as NT3, NT4 and brain derived 
      neutrophic factor (BDNF) as well as the corresponding receptors (NTRs). Different 
      members of NTRs are expressed during prostate cancer (PCa) progression, 
      suggesting their involvement in cell proliferation, anoikis protection and 
      malignancy. Therefore, we analyzed the expression of NTRs including NTRK1 (TrkA), 
      NTRK2 (TrkB), NTRK3 (TrkC) and p75 NGFR in a panel of 7 well-characterized PCa 
      cell lines and 12 cell derivatives from PC3 (4), DU145 (2), CWR22R (4) and LnCap 
      (2) cell lines possessing different proliferative/invasive capabilities. We 
      evaluated also the role of NGF, BDNF and NT3 in the modulation of cell migration 
      and invasion and, finally, the effects of a pan Trk inhibitor, CEP-701 which has 
      been included in some clinical trials for the treatment of PCa. We observed the 
      following: i) TrkA and TrkB expression was significantly higher in AR-negative 
      compared to AR-positive cells; ii) TrkA and TrkB expression was related to the 
      invasive capacity/malignancy of PCa cells; iii) p75 NGFR could be considered a 
      tumor suppressor gene which is present at high levels only in AR-positive cells; 
      and iv) that NGF and BDNF (targeting TrkA/p75 NTR and TrKB, respectively) induced 
      cell migration and this was inhibited by the CEP-701 treatment. In conclusion, 
      the malignancy of PCa seems to be accompanied by increased TrkA and TrkB 
      signaling (with a reduction of p75 NGFR expression) and CEP-701 could be used to 
      reduce the metastasis formation in advanced PCa. CEP-701 is a trademark of 
      Cephalon Inc., West Chester, PA, USA.
FAU - Festuccia, Claudio
AU  - Festuccia C
AD  - Department of Experimental Medicine, University of L'Aquila, I-67100 L'Aquila, 
      Italy. festucci@univaq.it
FAU - Muzi, Paola
AU  - Muzi P
FAU - Gravina, Giovanni Luca
AU  - Gravina GL
FAU - Millimaggi, Danilo
AU  - Millimaggi D
FAU - Speca, Silvia
AU  - Speca S
FAU - Dolo, Vincenza
AU  - Dolo V
FAU - Ricevuto, Enrico
AU  - Ricevuto E
FAU - Vicentini, Carlo
AU  - Vicentini C
FAU - Bologna, Mauro
AU  - Bologna M
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Furans)
RN  - 0 (Indoles)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Androgen)
RN  - DO989GC5D1 (lestaurtinib)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Carbazoles/*pharmacology
MH  - Cell Line, Tumor
MH  - Enzyme Inhibitors/pharmacology
MH  - Furans
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Male
MH  - Neoplasm Invasiveness
MH  - Nerve Growth Factors/pharmacology
MH  - Prostatic Neoplasms/*pathology
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Receptor, trkA/*antagonists & inhibitors/genetics
MH  - Receptors, Androgen/analysis
EDAT- 2006/12/05 09:00
MHDA- 2007/02/01 09:00
CRDT- 2006/12/05 09:00
PHST- 2006/12/05 09:00 [pubmed]
PHST- 2007/02/01 09:00 [medline]
PHST- 2006/12/05 09:00 [entrez]
PST - ppublish
SO  - Int J Oncol. 2007 Jan;30(1):193-200.