Characterization of the cholinergic neuronal differentiation of the human neuroblastoma cell line LA-N-5 after treatment with retinoic acid.
Analysis of the molecular factors that control cellular differentiation in mammalian embryos is difficult due to the small amount of material available from embryos and their inaccessibility during gestation. One way to circumvent these limitations is to use model systems that allow the study of differentiation in vitro. In this study we have characterized the response of a human neuroblastoma cell line, LA-N-5, to the differentiation-inducing agent, all-trans retinoic acid (RA) using 23 markers that are characteristic of neural crest cells and some of their derivatives. Following induction with RA, the neural crest-like LA-N-5 cells undergo differentiation into cholinergic neurons with increased expression of a variety of neural-specific markers including neurofilaments, growth associated protein-43, tetanus toxin binding sites, receptors for neurotrophic factors, neuropeptides, choline acetyl transferase, vesicular acetylcholine transporter, and acetylcholinesterase with a concomitant decrease in the expression of non-neuronal markers. These results provide the basis for the use of retinoic acid-induced differentiation of LA-N-5 cells as a model system to study molecular events associated with the differentiation of cholinergic neurons.
Hill
D P
DP
Department of Pediatrics, Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University Medical Center, Indianapolis 46202-5225, USA.
Robertson
K A
KA
D000109:Acetylcholine / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014212:Tretinoin; D000109:Acetylcholine