Retinoic acid induces functional c-Ret tyrosine kinase in human neuroblastoma.
After the treatment of human neuroblastoma SH-SY5Y cells with retinoic acid for 24 h, the expression of c-Ret receptor tyrosine kinase was greatly elevated. Treatment of SH-SY5Y cells with glial cell line-derived neurotrophic factor under serum-free conditions after incubation of cells with retinoic acid resulted in the phosphorylation of c-Ret receptor tyrosine kinase, with subsequent morphological changes that included formation of neurites and rounding of cell bodies within 24-48 h. The number of neurite-bearing cells decreased with increasing concentrations of mitogen-activated protein kinase-specific and phosphatidylinositol 3-kinase inhibitors. These observations suggest that retinoic acid induces the expression of glial cell line-derived neurotrophic factor-responsive c-Ret receptor tyrosine kinase and that a glial cell line-derived neurotrophic factor-c-Ret receptor tyrosine kinase-induced signal transduction system that might be involved in neurite outgrowth via pathways that include phosphatidylinositol 3-kinase and mitogen-activated protein kinase.
Yamada
Shigeru
S
Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), Aomi Kohtoh-ku, Tokyo, Japan.
Nomura
Takashi
T
Uebersax
Lorenz
L
Matsumoto
Kayo
K
Fujita
Satoshi
S
Miyake
Masato
M
Miyake
Jun
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051100:Glial Cell Line-Derived Neurotrophic Factor; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; D014212:Tretinoin; D020794:Receptor Protein-Tyrosine Kinases