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Dependence receptors as links between apoptosis, nervous system development and control of tumorigenesis

Bulletin du Cancer. Volume 87, Number 7-8, 537-41, Numéro double 7 - 8, Juillet -Août 2000, Synthèses

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Author(s) : Patrick Mehlen, Dale E. Bredesen

Summary : The dependence receptor notion was based on the observation that the effects of a number of receptors that function in both nervous system development and tumorigenesis (especially metastasis) cannot be explained simply by a positive effect of signal transduction induced by ligand binding. Receptors such as the common neurotrophin receptor p75NTR, the androgen receptor (AR), DCC (deleted in colorectal cancer), and RET (rearranged during transfection) demonstrate effects that are more adequately explained when these are considered to be dependence receptors. These receptors show two distinct forms of signal transduction depending on their respective ligand availability: in the presence of their ligands, they transduce a signal for either proliferation or differentiation; however, they are not inactive in the absence of their ligands, but rather induce an active signal for cell death. Such receptors thus create a cellular state of dependence on their ligands, the loss of ligand availability inducing cell suicide or enhancing the likelihood of cellular suicide. This new concept is reviewed here enlightening the molecular mechanisms of these receptors and their potential relevance in vivo in the development of the nervous system and in the control of tumorigenesis.

Keywords : apoptosis, dependence receptors, tumorigenesis, nervous system.


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