title: A novel function of the human oncogene Stil: Regulation of PC12 cell toxic susceptibility through the Shh pathway.
abstract: The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in vertebrate species. Here, we report new findings of Stil in the regulation of toxic susceptibility in mammalian dopaminergic (DA)-like PC12 cells. RNAi-mediated knockdown of Stil expression did not affect the survival of proliferating PC12 cells but caused a significant amount of cell death in differentiated neurons after toxic drug treatment. In contrast, overexpression of Stil increased toxic susceptibility only in proliferating cells but produced no effect in mature neurons. Exogenetic inactivation or activation of the Sonic hedgehog (Shh) signaling transduction mimicked the effect of Stil knockdown or overexpression in regulation of PC12 cell toxic susceptibility, suggesting that Stil exerts its role through the Shh pathway. Together, the data provide evidence for novel functions of the human oncogene Stil in neural toxic susceptibility.
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Aprell L
authors.initials: AL
authors.lastname: Carr
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China 300457.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Audrey
authors.initials: A
authors.lastname: Drewing
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lee
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China 300457.
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D009857:Oncogenes; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009498:Neurotoxins; C071236:STIL protein, human; D016627:Oxidopamine; D053148:Caspase 3