RESUMEN
Prostaglandin F(2alpha) (PGF(2alpha)), a mitogen for Swiss 3T3 cells, triggers 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-diacylglycerol (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(2alpha), but not OAG, increases cyclin D1 expression with no mitogenic response. Finally, OAG, in the presence of orthovanadate (Na(3)VO(4)) or TGF(beta1), induces DNA synthesis. Thus, it appears that PGF(2alpha) triggers cyclin D1 expression via two independent signaling events that complement with TGF(beta1)-triggered events to induce DNA synthesis.
Asunto(s)
Ciclina D1/biosíntesis , Dinoprost/farmacología , Mitógenos/farmacología , Células 3T3 , Animales , Ciclo Celular/efectos de los fármacos , Ciclina D1/genética , Replicación del ADN/efectos de los fármacos , Regulación de la Expresión Génica , Glicéridos/farmacología , Ionóforos/farmacología , Ratones , Modelos Biológicos , Proteína Quinasa C/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/farmacología , Vanadatos/farmacologíaRESUMEN
Leukaemia inhibitory factor (LIF) stimulates cellular DNA synthesis in confluent quiescent Swiss 3T3 cells. Insulin and prostaglandin E1 (PGE1), which fail to stimulate DNA synthesis alone, potentiate this effect. Prostaglandin F2alpha (PGF2alpha), which is mitogenic in these cells, enhances the effect of LIF on DNA synthesis. TGFbeta1 increases the effect of PGF2alpha but not that of LIF. R-59022, a diacylglycerol kinase inhibitor which increases protein kinase C (PKC) activity, enhances only the PGF2alpha response. 13-Tetradecanoyl-12-phorbolacetate-mediated PKC depletion prevents the action of PGF2alpha but not that of LIF, nor the PGF2alpha potentiation of LIF-stimulated DNA synthesis. 1-Oleoyl-2acetylglycerol, a PKC and tyrosine kinase (TK) activator which mimics some of the PGF2alpha effects, enhances only LIF-induced DNA synthesis in cells possessing intact PKC activity. These results suggest that stimulation of DNA synthesis by LIF, as well as its enhancement by PGF2alpha, may occur via a signalling pathway independent of PKC activation.