EXPRESSION OF WILMS-TUMOR SUPPRESSOR GENE (WT1) IN TERM HUMAN TROPHOBLAST - REGULATION BY CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE

The Wilms' tumor suppressor gene (WT1) which is deleted in some Wihms' tumors, encodes a zinc finger transcription factor. We studied WT1 me ssenger ribonucleic acid (mRNA) in human term placenta and cytotrophob lasts differentiating into syncytiotrophoblasts in vitro by RT-PCR. Th e results suggest that WT1 mRNA is expressed in the trophoblasts in a cell-specific fashion. WT1 mRNA expression has been observed to declin e remarkably in trophoblast cells after 72 h, when these cells are mor phologically differentiated into multinucleated syncytiotraphoblasts. As it is well known that cAMP as a second messenger plays a significan t role in cellular proliferation and differentiation of placental cell s, we examined the effect of 8-bromo-cAMP on WT1 mRNA expression in un differentiated cytotrophoblasts and differentiated syncytiotrophoblast s. We observed that cAMP enhanced WT1 mRNA expression in cytotrophobla sts, but remained ineffective in altering WT1 mRNA in syncytiotrophobl asts. In summary, the results of this investigation demonstrate that t he WT1 gene is developmentally regulated during trophoblast differenti ation. An involvement of the cAMP-mediated system in regulating the WT 1 gene in the trophoblast is suggested.