Prostaglandin F-2 alpha (PGF(2 alpha)) induces cyclin D1 expression and DNA synthesis via early signaling mechanisms in Swiss mouse 3T3 cells

Prostaglandin F-2 alpha (PGrF(2 alpha)), a mitogen for Swiss 3T3 cells, tri ggers cyclin D1 mRNA/protein expression prior to cellular entry into the S phase, but fails to raise cdk4 or cyclin D3 levels, while 1-oleoyl-2-diacyl glycerol (OAG), a protein kinase C (PKC) and tyrosine kinase (TK) activator , induces only cyclin D1 expression with no mitogenic response. In contrast , in PKC-depleted or -inhibited cells, PGF(2 alpha), but not OAG, increases cyclin D1 expression with no mitogenic response. Finally, OAG, in the pres ence of orthovanadate (Na3VO4) or TGF(beta 1), induces DNA synthesis. Thus, it appears that PGF(2 alpha) triggers cyclin D1 expression via two indepen dent signaling events that complement with TGF(beta 1)-triggered events to induce DNA synthesis. (C) 2000 Academic Press.