Expression, regulation, and function of PAX8 in the human placenta and placental cancer cell lines

Elisabetta Ferretti, Franco Arturi, Tiziana Mattei, Angela Scipioni, Gianluca Tell, Emanuele Tosi, Ivan Presta, Roberta Morisi, Ludovic Lacroix, Alberto Gulino, Diego Russo, Giuseppe Damante, Sebastiano Filetti

Research output: Contribution to journalArticlepeer-review

Abstract

Pax proteins are transcriptional regulators that control a variety of developmental decisions in vertebrates. During development, the paired-box gene 8 (PAX8) is expressed in the thyroid, kidney, and several areas of the central nervous system. It is also expressed in the adult thyroid gland, where it mediates thyroid stimulating hormone (TSH) induced modulation of the expression of important genes, such as those encoding thyroglobulin, thyroperoxidase, and the sodium/iodide symporter (NIS). Thus far placental expression of PAX8 has been described only in mice. In the present study, we show that PAX8 is also expressed in the human placenta at term. In an in vitro model of placental cancer, the JAR choriocarcinoma cell line, human chorionic gonadotropin (hCG) increased levels of PAX8 mRNA and protein, and gel-retardation assays indicated that the up-regulation of PAX8 protein expression is associated with an increase in its DNA-binding activity. The effects of hCG were mimicked by forskolin, indicating that they are cAMP-dependent. Levels of mRNA for the Wilms' tumor 1 (WT1) and NIS genes were increased in JAR cells by hCG treatment while overexpression of PAX8 increased only levels of WT1 mRNA. In cells transfected with PAX8-specific small interfering RNA, the stimulatory effects of hCG on WT1 mRNA levels were abolished, but hormonal enhancement of NIS mRNA levels was unchanged. These findings indicate that, in JAR cells, hCG activates a cAMP-dependent pathway that can up-regulate WT1 expression through PAX8.

Original languageEnglish
Pages (from-to)4009-4015
Number of pages7
JournalEndocrinology
Volume146
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • hCG
  • JAR cells
  • NIS
  • PAX8
  • Placenta
  • WT1

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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