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

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‐β‐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 (IP3) production and PKC‐α membrane translocation. After estradiol treatment the increase of IP3 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‐α presence on the membranes appeared unchanged in MCF7 cells. The PLC inhibitors, neomycin and U73,122, and PKC‐α 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 β‐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‐α pathway is present. The reported results indicate that the DNA synthesis stimulation by β‐estradiol requires the estrogen receptor and utilises one or more activated pathways in dependence on the cell equipment. © 2001 Wiley‐Liss, Inc.