β‐estradiol stimulation of DNA synthesis requires different PKC isoforms in HepG2 and MCF7 cells

Abstract

The role exerted by protein kinase C (PKC) on estrogen-induced DNA synthesis has been investigated in hepatic and mammary gland cells, HepG2 and MCF7. 17-beta-estradiol stimulated DNA synthesis in HepG2 and MCF7 cells, maximal effect occurring at 10 nM. DNA synthesis stimulation was prevented by anti-estrogen ICI 182,780 and by inhibitor of PKC, Ro 31-8220. The rapid estradiol effects in MCF7 cells were determined by following the inositol trisphosphate (IP(3)) production and PKC-alpha membrane translocation. After estradiol treatment the increase of IP(3) production, prevented by anti-estrogen or by phospholipase C (PLC) inhibitor (neomycin), was present in MCF7 cells. In MDA cells, devoid of estrogen receptor, no effect was observed. The PKC-alpha presence on the membranes appeared unchanged in MCF7 cells. The PLC inhibitors, neomycin and U73,122, and PKC-alpha down regulator, phorbol 12-myristate 13-acetate (PMA), were able to prevent estradiol-induced DNA synthesis in hepatoma cells, but ineffective in mammary cells; wortmannin, an inhibitor of phosphoinositide 3-kinases (PI3-K), blocked DNA synthesis in both cell lines. These data show that beta-estradiol, via an estrogen receptor-mediated mechanism, activates more signal transduction pathways, and consequently different PKC isoforms in two responsive cell lines. In both cell lines PI3-K/PKC pathway is functional to the estrogen regulation of DNA synthesis, whereas in HepG2 cells the parallel involvement of the PLC/PKC-alpha pathway is present. The reported results indicate that the DNA synthesis stimulation by beta-estradiol requires the estrogen receptor and utilises one or more activated pathways in dependence on the cell equipment.

Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

“…The mechanism by which E2 exerts proliferative properties has been assumed to be exclusively mediated by ERα-induced rapid membrane-starting actions (Marino et al, 1998;Castoria et al, 1999;Lobenhofer et al, 2000;Marino et al, 2001;Castoria et al, 2001;Marino et al, 2002;Marino et al, 2003;Acconcia et al, 2005b), whereas E2 induces cell death through ERβ nongenomic signaling (Acconcia et al, 2005b). In the nervous system, E2 influences neural functions (e.g., cognition, behavior, stress responses, and reproduction) in part inducing such rapid responses (Farach-Carson and Davis, 2003;Losel et al, 2003).…”

“…In the nervous system, E2 influences neural functions (e.g., cognition, behavior, stress responses, and reproduction) in part inducing such rapid responses (Farach-Carson and Davis, 2003;Losel et al, 2003). In the liver, rapid E2-induced signals are deeply linked to the expression of LDL-receptor and to the decreased cholesterol-LDL levels in the plasma (Marino et al, 2001;Distefano et al, 2002). An important mode of E2-mediated atheroprotection is linked to E2 capability to rapidly activate endothelial NOS and NO production (Chambliss et al, 2002;Simoncini et al, 2000).…”

Impact of PKCδ on estrogen receptor localization and activity in breast cancer cells

“…Furthermore, activation of PKC by phorbol esters downregulates ERa in estrogen-dependent MCF-7 breast cancer cells (Ree et al, 1991;Tzukerman et al, 1991). PKCa has been attributed a particular role in ERa function in T47D cells (Tonetti et al, 2000), osteoblasts (Longo et al, 2004) and HepG2 cells (Marino et al, 2001).…”

Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

“…The causal role of these nongenotropic estrogen-signaling pathways and their correlation with the classical, gene transcription-mediated actions of these hormones are far from being understood. For example, although some reports indicate a central role for ERKs and protein kinase C-␣ signaling in estrogen regulation of cell cycle progression (Castoria et al, 1999;Manole et al, 2001;Marino et al, 2001), other authors have shown cell cycle effects of these hormones independently from these cascades. Furthermore, a growing body of evidence suggests the existence of cross talk between estrogen receptors and other signaling pathway effectors (Tolon et al, 2000;Coleman and Smith, 2001).…”