β-estradiol stimulation of DNA synthesis requires different PKC isoforms in HEPG2 and MCF7 cells

Maria Marino, Enza Distefano, Simona Caporali, Gianna Ceracchi, Valentina Pallottini, Anna Trentalance

Research output: Contribution to journalArticle

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-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.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalJournal of Cellular Physiology
Volume188
Issue number2
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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