INDUCTION OF AROMATASE GENE-EXPRESSION IN HUMAN PLACENTAL CHORIOCARCINOMA (JAR) CELLS BY PHORBOL ESTERS

The expression of aromatase in JAR cells, human placental choriocarcinoma cells, was found to be induced by the treatment of phorbol 12,13-diacetate (PDA), phorbol 12,13-didecanoate (PDD), or phorbol 12-myristate 13-acetate (TPA), but not 4 alpha-phorbol, 12,13-didecanoate (4 alpha PDD). At 1 mu M or higher concentrations, these phorbol esters increased the level of aromatase mRNA and aromatase activity in a dose- and time-dependent fashion. Since the rates of the decrease of aromatase mRNA in phorbol ester treated and untreated cells were not significantly different in the presence of actinomycin D, the induction was not due to an increase in the stability of aromatase mRNA, but rather due to an increase in the synthesis of aromatase mRNA. The stimulation was not inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). It is thought that the induction either follows a protein kinase C-independent manner or results from a down-regulation of protein kinase C pathway. Studies from several laboratories have revealed that the regulation of the expression of aromatase in estrogen-producing cells involves very complex processes. The apparent induction of aromatase expression in JAR cells by phorbol esters represent a mechanism modulating estrogen production in human placental choriocarcinoma cells, that may or may not be utilized in other estrogen-producing cells.