Potential role of WSB1 isoforms in growth and survival of neuroblastoma cells.
BACKGROUND
WD repeat and SOCS box containing protein 1 (WSB1) generates three isoforms that were found to play a role in cancer cell growth and tumor progression. We have studied their expression in neuroblastoma (NB).


METHODS
The behavior of the expression levels of the WSB1 isoforms was analyzed in NB cell lines, in an in vivo NB xenograft mouse model, and in primary NB tumors using real-time PCR. Effective WSB1 small interfering RNAs were transfected into cultured NB cell lines, and cell viability was analyzed using XTT assay and flow cytometry.


RESULTS
A significant predominance of the WSB1 isoform 3 (WSB1(3)) expression level was demonstrated in all NB systems examined. Correspondingly, combination of WSB1(3) silencing together with WSB1 isoforms 1+2 silencing in NB cells showed reduced growth, enhanced apoptosis rate, and increased sensitivity to chemotherapeutic agents, specifically related to low expression of WSB1(3).


CONCLUSIONS
Our results point to a possible differential role of WSB1 isoforms in NB and suggest WSB1(3) as a target for therapy in NB.
1] Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Keren
K
Shichrur
1] Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Galina
G
Feinberg-Gorenshtein
Pediatric Hematology Oncology Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Drorit
D
Luria
Pediatric Hematology Oncology Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Shifra
S
Ash
1] Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel [3] Pediatric Hematology Oncology Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Isaac
I
Yaniv
1] Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel [3] Pediatric Hematology Oncology Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Smadar
S
Avigad
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D011506:Proteins; C120287:WSB1 protein, human