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J Biol Chem, Vol. 274, Issue 23, 16451-16460, June 4, 1999
Brain-derived Neurotrophic Factor Promotes Survival and
Chemoprotection of Human Neuroblastoma Cells
David S.
Middlemas,
Brenda K.
Kihl,
Junfang
Zhou, and
Xiaoyan
Zhu
From the Department of Molecular Pharmacology, St. Jude
Children's Research Hospital, Memphis, Tennessee 38105-2794
Brain-derived neurotrophic factor (BDNF) promotes
neuronal survival and protection against neuronal damage. We addressed
whether BDNF might promote survival and chemoprotection in
neuroblastoma (NB) using a drug-sensitive human NB cell line.
All-trans-retinoic acid (ATRA) induces a striking phenotypic
differentiation of NB1643 cells, and exogenous BDNF treatment promotes
survival of these differentiated cells. ATRA induces TRKB expression,
and exogenous BDNF stimulates both autophosphorylation of TRKB and
induction of the immediate early gene, FOS, in these cells.
BDNF mRNA is expressed in NB1643 cells. Because the
time course of TRKB induction closely parallels phenotypic
differentiation of these cells, it seems probable that ATRA induces
differentiation of NB1643 cells by establishing an autocrine loop
involving BDNF and TRKB. Exogenous BDNF treatment resulted in a further
increase in neurite outgrowth, which again suggests that an autocrine
loop is involved in differentiation of NB1643 cells in response to
ATRA. We then tested whether BDNF might afford drug resistance in NB
and found that BDNF does indeed protect in this NB model against
cisplatin, a DNA-damaging agent actually used in the treatment of
NB.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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