Human neuroblastomas with unfavorable biologies express high levels of brain-derived neurotrophic factor mRNA and a variety of its variants

The expression of human brain-derived neurotrophic factor (BDNF) was invest igated in 16 primary human neuroblastomas with favorable biologies, 15 with unfavorable biologies. and in human neuroblastoma cell lines. We demonstra ted higher expressions of human BDNF mRNA in neuroblastomas with unfavorabl e biologies and with N-myc amplification than in those with favorable biolo gies. For the first time we revealed the composition of splice variants of human BDNF mRNA and analyzed their expression in neuroblastomas by reverse transcription polymerase chain reaction (RT-PCR). Interestingly, human BDNF mRNA consisted of at least six isoforms, four isoforms resembling those of rat BDNF mRNA, a human-specific isoform and a new isoform, The expression of four isoforms were more prominent in tumors with unfavorable biologies t han in those with favorable biologies (P < 0.05). As previously we had repo rted, over 80% of the primary tumors expressed either the full-length form of BDNF receptor, TRKB, or a truncated form of TRKB lacking the tyrosine ki nase domain. The full-length TRKB was predominantly detected in tumors with unfavorable biologies, and the truncated one in those with favorable biolo gies. These results suggest that an autocrine and/or paracrine mechanism in volving BDNF may stimulate signal transduction via TRKB receptors rich in n euroblastomas with unfavorable biologies, resulting in an aberrant survival of tumor cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .