PMID- 10637439
OWN - NLM
STAT- MEDLINE
DCOM- 20000224
LR  - 20071114
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 6
IP  - 12
DP  - 1999 Dec
TI  - Neurotrophin dependence mediated by p75NTR: contrast between rescue by BDNF and 
      NGF.
PG  - 1222-7
AB  - During development, neurons pass through a critical phase in which survival is 
      dependent on neurotrophin support. In order to dissect the potential role of 
      p75NTR, the common neurotrophin receptor, in neurotrophin dependence, we 
      expressed wild-type and mutant p75NTR in cells that do not express endogenous 
      p75NTR or Trk family members (NIH3T3). Expression of wild-type p75NTR created a 
      state of neurotrophin dependence: cells could be rescued by nerve growth factor 
      (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3), but 
      not by a mutant NGF that binds well to Trk A but poorly to p75NTR. Similarly, 
      expression of p75NTR in human prostate cancer cells in culture rendered a 
      metastatic tumor cell line (PC-3) sensitive to the availability of neurotrophins 
      for survival. Moreover, expression of mutant p75NTR's in another 
      neurotrophin-insensitive cell line (HEK293T) showed that a domain within the 
      intracellular domain governs alternate responses to neurotrophins: the carboxy 
      terminus of the intracellular domain of p75NTR including the sixth alpha helix 
      domain is necessary for rescue by BDNF, but not NGF. These results, when 
      considered with previous studies of the timing of p75NTR expression, support the 
      hypothesis that p75NTR is a mediator of neurotrophin dependence during the 
      critical phase of developmental cell death and during the progression of 
      carcinogenesis in prostate cancer.
FAU - Rabizadeh, S
AU  - Rabizadeh S
AD  - Program on Aging, The Burnham Institute, La Jolla, California, CA 92037, USA.
FAU - Rabizadeh, S
AU  - Rabizadeh S
FAU - Ye, X
AU  - Ye X
FAU - Wang, J J
AU  - Wang JJ
FAU - Bredesen, D E
AU  - Bredesen DE
LA  - eng
GR  - CA69381/CA/NCI NIH HHS/United States
GR  - NS100661/NS/NINDS NIH HHS/United States
GR  - T32AG00252/AG/NIA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Apoptosis
MH  - Binding Sites
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carcinoma/metabolism
MH  - Cell Survival
MH  - Humans
MH  - Male
MH  - Mice
MH  - Nerve Growth Factor/*metabolism
MH  - Prostatic Neoplasms/*metabolism
MH  - Protein Structure, Secondary
MH  - Receptors, Nerve Growth Factor/chemistry/genetics/*metabolism
MH  - Sequence Deletion
MH  - Signal Transduction
EDAT- 2000/01/19 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/19 09:00
PHST- 2000/01/19 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/19 09:00 [entrez]
AID - 10.1038/sj.cdd.4400614 [doi]
PST - ppublish
SO  - Cell Death Differ. 1999 Dec;6(12):1222-7. doi: 10.1038/sj.cdd.4400614.