Partial involvement of c-jun protooncogene in growth enhancing and cytotoxic effects of lithium in vitro.
The AP-1 transcription factor is comprised of homo- and heterodimers of the Fos and Jun families of proteins. Literature reports indicate that AP-1 is activated in lithium treated mammalian cells suggesting a role in lithium induced growth stimulation and apoptosis. In these studies, an antisense c-jun plasmid blocked the stimulation of HL-60 cell growth by lithium. Furthermore, antisense c-jun caused a 60% reduction in cell viability at 48 hr post-transfection but did not influence DNA fragmentation in the presence of lithium. The levels of c-jun mRNA, as determined by RT-PCR, were not affected by lithium treatment. Nevertheless, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) blocked the induction of apoptosis by lithium suggesting the involvement of the protein kinase C (PKC) signaling pathway. In RAJI cells, antisense c-jun mimicked lithium by inhibiting cell proliferation with only a marginal loss in cell viability. This study therefore suggests that PKC is involved in the effects of lithium on cells in culture and provides evidence for differential effects of antisense c-jun on hemotopoietic lineages.
Shai
L J
LJ
Department of Biochemistry, University of the North, Private Bag X1106, Sovenga, 0727, South Africa.
Abotsi
E K
EK
Tyobekai
E M
EM
Wachira
J M
JM
D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016755:Proto-Oncogene Proteins c-jun; D008094:Lithium