Identification and characterisation of STMN4 and ROBO2 gene involvement in neuroblastoma cell differentiation.
To better understand neuroblastoma differentiation, we used microarray analysis to identify common gene expression changes from three differentiation models. This revealed STMN4 and ROBO2 to be consistently up-regulated in differentiated neuroblastoma cells induced by chromosome 1 transfer, MYCN knockdown, and 9-cis retinoic acid (9cRA). Furthermore, stable expression of transfected STMN4 or ROBO2 induced differentiation in IMR-32 cells. STMN4 and ROBO2 expression also increased in other 9cRA-induced differentiated neuroblastoma cell lines. Of clinical importance is that neuroblastoma patients with higher tumour mRNA expression of STMN4 and ROBO2 had better progression-free survival. This study highlights the importance of STMN4 and ROBO2 during neuroblastoma differentiation.
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Pei-Ju
PJ
Sung
Nidal
N
Boulos
Michael John
MJ
Tilby
William David
WD
Andrews
Robert Frank
RF
Newbold
Deborah Anne
DA
Tweddle
John
J
Lunec
D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D050777:Stathmin / Q000235:genetics*; D000097905:Roundabout Proteins
D009414:Nerve Growth Factors; D011971:Receptors, Immunologic; D050777:Stathmin; C498890:ROBO2 protein, human; D000097905:Roundabout Proteins; C491795:STMN4 protein, human