IGF-II enhances Trichostatin A-induced TGF beta 1 and p21(Waf1,Cip1,Sdi1) expression in Hep3B cells

Cell growth and division are controlled through the actions of cyclin-depen dent kinases (CDKs) and cyclin dependent kinase inhibitors (CKIs). Treatmen t 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 actio ns of TGF beta 1, Latent TGF beta 1 can be activated by the M6P/IGF2R. In t he present study we have examined the effect of TSA on members of the IGF a xis, the CKIs p21 and p27, and also TGF beta 1 in Hep3B cells. The only mem ber of the IGF axis to be affected by treatments was IGF2, Expression of an other gene from the same chromosomal location, H19, was also affected. TGF beta 1 expression was greatly enhanced by TSA. In addition, both CKIs, p22 and p27, were upregulated by TSA. Effects of adding IGF-II or TGF beta 1 to TSA-treated cells on p21 induction were examined. The results show that th e induction of p21 by TSA can be modulated by additions of IGF-II whereas a ddition of TGF beta 1 affects its own expression but not p21. In conclusion , the results indicate that the induction of p21 and cell growth arrest cau sed by Trichostatin A may involve multiple signaling pathways. (C) 1999 Aca demic Press.