Int J Biochem Mol Biol 2012;3(1):28-35
Original Article
Rapamycin induces the anti-apoptotic protein survivin in neuroblastoma
Ayman Samkari, Zachary A Cooper, Michael P Holloway, Jiebin Liu, Rachel A Altura
Department of Pediatrics, Division of Hematology-Oncology, The Warren Alpert Medical School of Brown University and Rhode Island Hospital,
593 Eddy Street, Providence, RI, 02903, USA
Received January 6, 2012; accepted January 25, 2012; Epub February 10, 2012; Published March 30, 2012
Abstract: Neuroblastoma is the most common solid tumor of infancy, accounting for 15% of all cancer cell deaths in children. Expression of
the anti-apoptotic protein survivin in these tumors correlates with poor prognostic features and resistance to therapy. The mammalian target of
rapamycin (mTOR) protein is being explored as a potential therapeutic target in patients with this disease. The objective of this study was to
test the hypothesis that rapamycin regulates survivin expression and function in neuroblastoma cells. To explore this hypothesis, we treated
two different neuroblastoma lines (NB7, NB8) and a well-characterized control lung cancer cell line, A549, with varying doses of rapamycin
(0.1-10µM) for serial time points (2-48 hours). RNA and protein expression levels were then evaluated by quantitative RT-PCR and western
blotting, respectively. Cell proliferation and apoptosis were assayed by WST-1 and Annexin V. The results showed a rapamycin-dependent
increase in survivin mRNA and protein levels in the neuroblastoma cell lines in a dose- and time-dependent fashion, while a decrease in
these levels was observed in control cells. Rapamycin inhibited cell proliferation in both A549 and neuroblastoma cells however
neuroblastoma cells had less apoptosis than A549 cells (9% vs. 20%). In summary, our results indicate that rapamycin induces expression of
the anti-apoptotic protein survivin in neuroblastoma cells which may protect these cells from programmed cell death. Induction of survivin by
rapamycin could therefore be a potential mechanism of neuroblastoma tumor cell resistance and rapamycin may not be an effective
therapeutic agent for these tumors. (IJBMB1201001).
Keywords: Survivin, neuroblastoma, rapamycin, mTOR, HSP90
Address all correspondence to:
Dr. Rachel A. Altura
Department of Pediatrics
Rhode Island Hospital
593 Eddy Street, MPS 126
Providence, RI 02903, USA.
Tel: 401-444-2502; Fax: 401-444-8845
E-mail: rachel_altura@brown.edu
Original Article
Rapamycin induces the anti-apoptotic protein survivin in neuroblastoma
Ayman Samkari, Zachary A Cooper, Michael P Holloway, Jiebin Liu, Rachel A Altura
Department of Pediatrics, Division of Hematology-Oncology, The Warren Alpert Medical School of Brown University and Rhode Island Hospital,
593 Eddy Street, Providence, RI, 02903, USA
Received January 6, 2012; accepted January 25, 2012; Epub February 10, 2012; Published March 30, 2012
Abstract: Neuroblastoma is the most common solid tumor of infancy, accounting for 15% of all cancer cell deaths in children. Expression of
the anti-apoptotic protein survivin in these tumors correlates with poor prognostic features and resistance to therapy. The mammalian target of
rapamycin (mTOR) protein is being explored as a potential therapeutic target in patients with this disease. The objective of this study was to
test the hypothesis that rapamycin regulates survivin expression and function in neuroblastoma cells. To explore this hypothesis, we treated
two different neuroblastoma lines (NB7, NB8) and a well-characterized control lung cancer cell line, A549, with varying doses of rapamycin
(0.1-10µM) for serial time points (2-48 hours). RNA and protein expression levels were then evaluated by quantitative RT-PCR and western
blotting, respectively. Cell proliferation and apoptosis were assayed by WST-1 and Annexin V. The results showed a rapamycin-dependent
increase in survivin mRNA and protein levels in the neuroblastoma cell lines in a dose- and time-dependent fashion, while a decrease in
these levels was observed in control cells. Rapamycin inhibited cell proliferation in both A549 and neuroblastoma cells however
neuroblastoma cells had less apoptosis than A549 cells (9% vs. 20%). In summary, our results indicate that rapamycin induces expression of
the anti-apoptotic protein survivin in neuroblastoma cells which may protect these cells from programmed cell death. Induction of survivin by
rapamycin could therefore be a potential mechanism of neuroblastoma tumor cell resistance and rapamycin may not be an effective
therapeutic agent for these tumors. (IJBMB1201001).
Keywords: Survivin, neuroblastoma, rapamycin, mTOR, HSP90
Address all correspondence to:
Dr. Rachel A. Altura
Department of Pediatrics
Rhode Island Hospital
593 Eddy Street, MPS 126
Providence, RI 02903, USA.
Tel: 401-444-2502; Fax: 401-444-8845
E-mail: rachel_altura@brown.edu
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