Mitogen-activated protein kinase activates human placental lactogen-B enhancer by an NF-IL6-dependent pathway

Anoop K. Brar, Randall G. Richards, You Hong Cheng, Brian Richardson, Yuki Kanda, Stuart Handwerger

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Computer analysis of the human placental lactogen-B (hPL-B) enhancer reveals two putative binding sites for the transcription factor NF-IL6, but the role of NF-IL6 in the regulation of the enhancer is unknown. Using gel mobility shift and supershift assays, we demonstrated that NF-IL6 binds to both enhancer sites. Transient transfection studies indicated that the transcription factor NF-IL6 stimulates hPL-B enhancer activity by 4.4-fold in primary cultures of human trophoblast cells and by 32.0- and 8.4-fold in JAR and BeWo choriocarcinoma cells, respectively. Overexpression of MEK (mitogen- activated protein [MAP] kinase kinase), which is known to stimulate phosphorylation of NF-IL6, induced a 3.6-fold increase in hPL-B enhancer activity. The induction by MEK was completely inhibited by an expression plasmid for a dominant/negative mutant of NF-IL6 or by mutation of the NF-IL6 binding sites on the enhancer. PD98059, an inhibitor of MEK, inhibited hPL release from cultured trophoblast cells by about 50%. Taken together, these results indicate that MAP kinase stimulates the hPL-B enhancer by an NF-IL-6- dependent pathway.

Original languageEnglish
Pages (from-to)47-52
Number of pages6
Issue number1
StatePublished - 2000


  • Gene regulation
  • Human placental lactogen
  • Mitogen-activated protein kinase
  • NF- IL6
  • Placenta


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