All-trans retinoic acid downregulates ALK in neuroblastoma cell lines and induces apoptosis in neuroblastoma cell lines with activated ALK.
Recently, gene amplification and gain-of-function mutations of ALK have been found in some neuroblastoma cell lines and clinical tumor samples. We have previously reported that knockdown of ALK by RNAi induced apoptosis in neuroblastoma cells with gene amplification of ALK. We report that all-trans retinoic acid (ATRA) downregulates ALK in neuroblastoma cell lines. Downregulation of ALK protein by ATRA was accompanied by apoptosis in neuroblastoma cells with gene amplification or gain-of-function mutation of ALK but not in neuroblastoma cells without these genetic alterations. These results suggest that ALK downregulation by ATRA might lead to apoptosis in neuroblastoma cells with activated ALK.
Futami
Hitoyasu
H
Growth Factor Division, National Cancer Center Research Institute, 5-1-1, Tsukiji-, Chuo-ku, Tokyo 104-0045, Japan.
Sakai
Ryuichi
R
D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005784:Gene Amplification; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D014212:Tretinoin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases