IGF-II enhances trichostatin A-induced TGFbeta1 and p21(Waf1,Cip1, sdi1) expression in Hep3B cells.
Cell growth and division are controlled through the actions of cyclin-dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CKIs). Treatment of cell lines with Trichostatin A leads to induction of one of these CKIs, p21, and growth arrest. Induction of p21 can also occur through the actions of TGFbeta1. Latent TGFbeta1 can be activated by the M6P/IGF2R. In the present study we have examined the effect of TSA on members of the IGF axis, the CKIs p21 and p27, and also TGFbeta1 in Hep3B cells. The only member of the IGF axis to be affected by treatments was IGF2. Expression of another gene from the same chromosomal location, H19, was also affected. TGFbeta1 expression was greatly enhanced by TSA. In addition, both CKIs, p21 and p27, were upregulated by TSA. Effects of adding IGF-II or TGFbeta1 to TSA-treated cells on p21 induction were examined. The results show that the induction of p21 by TSA can be modulated by additions of IGF-II whereas addition of TGFbeta1 affects its own expression but not p21. In conclusion, the results indicate that the induction of p21 and cell growth arrest caused by Trichostatin A may involve multiple signaling pathways.
Gray
S G
SG
Experimental Alcohol and Drug Addiction Research Section, Department of Clinical Neuroscience, Department of Clinical Neuroscience, Karolinska Institute, CMM, L8 01, Stockholm, S-171 76, Sweden.
Yakovleva
T
T
Hartmann
W
W
Tally
M
M
Bakalkin
G
G
Ekström
T J
TJ
D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology*; D008113:Liver Neoplasms; D011485:Protein Binding / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D017527:Receptor, IGF Type 2; D016212:Transforming Growth Factor beta; C012589:trichostatin A; D007335:Insulin-Like Growth Factor II; D006655:Histone Deacetylases