Down-regulation of achaete-scute complex homolog 1 (ASCL1) in neuroblastoma cells induces up-regulation of insulin-like growth factor 2 (IGF2).
Neuroblastoma (NB) is the most common extra-cranial solid pediatric tumor. The prognosis of patients with NB has been improved during the last decades. However, treatment results for patients with advanced tumor stages are still unsatisfying. NB cells are characterized by a high tendency for spontaneous or induced differentiation. During differentiation, down-regulation of the basic helix-loop-helix transcription factor achaete-scute complex homolog 1 (ASCL1) has been observed but the consequences of ASCL1 down-regulation have not been elucidated. We used RNA interference to knock-down ASCL1 in NB cells. DNA microarray analysis was used for the identification of ASCL1-regulated genes. Furthermore, conventional and quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used for validation of ASCL1-regulated genes. Down-regulation of ASCL1 influenced the expression of several genes. After down-regulation of ASCL1, we observed very high expression of insulin-like growth factor 2 (IGF2), a factor that is known to be induced during differentiation of NB cells. RT-PCR indicated up-regulation of multiple IGF2 transcript variants after ASCL1 knock-down. Our data suggest that the ASCL1-pathway is responsible for the up-regulation of IGF2 during NB differentiation.
Li
Jialing
J
Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Ernst Grube Str 40, 06097 Halle, Germany.
Neumann
Ingo
I
Volkmer
Ines
I
Staege
Martin Sebastian
MS
D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics*; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015854:Up-Regulation / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D007335:Insulin-Like Growth Factor II; D012333:RNA, Messenger; C065500:ASCL1 protein, human; C035170:IGF2 protein, human