USING THE ZEBRAFISH MODEL TO DETERMINE THE ROLE OF THE HACE1 TUMOUR SUPPRESSOR IN NORMAL DEVELOPMENT AND TUMOURIGENESIS

Abstract

HACE1 is a tumour suppressor gene located at human chromosome 6q21. HACE1 is downregulated in Wilms’ tumour as well as several other human cancers. Its role in normal development remains unknown. The zebrafish has established itself as a robust model for studying vertebrate development and human cancers. A zebrafish hace1 homologue has been identified. Whole mount in situ hybridization (WISH) assays and colocalization studies demonstrate conserved hace1 expression. Moreover, morpholino knockdown of hace1 reveals perturbed cardiac development and function. Transgenic zebrafish harboring either wild type or dominant negative mutated C876S (C876S DN) human HACE1 genes have been generated. DN zebrafish display increased apoptosis, both untreated and following irradiation-induced cellular damage. There was no difference in cell cycle progression between wild type embryos and C876S DN. Further characterization of the HACE1 transgenic zebrafish model will serve to better our understanding of the role of human HACE1 in normal development and tumourigenesis.