Expression and function of the homeodomain-containing protein Hex in thyroid cells

The homeodomain-containing protein Hex (also named Prh) is expressed in pri mitive endoderm (during the early phases of development), in some endoderm- derived tissues and in endothelial and hematopoietic precursors, Hex expres sion is extinguished during terminal differentiation of endothelial and hem atopoietic cells as well as in adult lung. Previous Investigations have dem onstrated that Hex is expressed during early thyroid gland development. No information has been reported on Hex expression In adult thyroid gland or o n the function of this protein in follicular thyroid cells. These issues re present the focus of the present study, We demonstrate that Hex mRNA is pre sent in rat and human adult thyroid gland as well as in differentiated foll icular thyroid cell lines. In FRTL-5 cells TSH reduces Hex expression. In t hyroid cell lines transformed by several oncogenes Hex expression is comple tely abolished, By using co-transfection assays we demonstrate that Hex is a repressor of the thyroglobulin promoter and that it is able to abolish th e activating effects of both TTF-1 and Pax8. These data would suggest that Hex may play an important role in thyroid cell differentiation. Protein-DNA interaction experiments indicate that Hex is able to bind sites of the thy roglobulin promoter containing either the core sequence 5'-TAAT-3' or 5'-CA AG-3'. The DNA binding specificity of the Hex homeodomain, therefore, is mo re 'relaxed' than that observed in the majority of other homeodomains.