1. ¹Cell & Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
2. ²The Second Affiliated Hospital of China Medical University, Shenyang, China
3. ³Department of Pediatrics, Korea University Anam Hospital, South Korea

Correspondence: C J Thiele, Cell & Molecular Biology Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive MSC-1928, Bldg. 10/CRC 1-3940, Bethesda, MD 20892, USA. Tel: +1 301 496 1543; Fax: +1 301 451 7052; E-mail: ct47a@nih.gov

Received 14 November 2005; Revised 2 May 2006; Accepted 3 May 2006; Published online 16 June 2006.

Abstract

Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells.