Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells

Sarit Freimann, Ido Ben-Ami, Ada Dantes, Leah Armon, Avital Ben Ya'cov-Klein, Raphael Ron-El, Abraham Amsterdam

Research output: Contribution to journalArticlepeer-review

Abstract

We have demonstrated previously that the synthesis of epiregulin and amphiregulin, of the EGF-like growth factor family, is stimulated by luteinizing hormone in human follicular (granulosa) cells obtained from in vitro fertilization program. In the present work, we demonstrate that H89, a PKA inhibitor, attenuated the expression of these growth factors both in the mRNA and the protein levels, suggesting PKA involvement in this signaling pathway. SV40-transformed human granulosa cells showed higher basal levels of epiregulin and amphiregulin than normal cells, which were still elevated following cAMP stimulation by Forskolin. Cleavage by a disintegrin and metalloproteinases (ADAMs) is essential for activation of these growth factors, allowing their interaction with EGF receptor. Expression of ADAMTS1 and ADAM12 was downregulated by cAMP in normal, but not in SV40-transformed cells, suggesting that in normal cells epiregulin and amphiregulin activity is downregulated by a feedback mechanism that may be lost in SV40-transformed cells and their loss of downregulation may be involved in the development of ovarian tumors.

Original languageEnglish
Pages (from-to)935-943
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume333
Issue number3
DOIs
StatePublished - 5 Aug 2005

Keywords

  • Amphiregulin
  • Desensitization
  • Epiregulin
  • Metalloproteinase
  • Ovary
  • SV40 oncogene

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