Long-term EGF/serum-treated human thyrocytes mimic papillary thyroid carcinomas with regard to gene expression

Constitutive activation of the RAS/RAF/MAPK pathway has been found in different tumor types including papillary thyroid carcinomas (PTCs). To get more insight into genes primarily regulated in the human tumor cells, an in vitro model was developed in which primary cultures of human thyrocytes were treated for different times with epidermal growth factor and serum (EGF/serum), which stimulate the MAPK cascade. Gene expression profiles were obtained by microarrays and compared to the expression profiles of PTCs. An evolution from short-term to long-term EGF/serum-treated cells was found, i.e., a program change showing a distinction between gene expression profiles of short-term and long-term EGF/serum-treated cells. The late pattern of EGF/serum stimulated cells converges to the pattern of PTCs. Comparison of these two types of cells with cAMP activated cells, from thyroid-stimulating hormone-treated thyrocytes and autonomous adenomas, showed distinct gene expression profiles for the two pathways. For the two models, an overlap was found in a number of genes which were early induced in vitro but down-regulated later in vitro and in the in vivo tumors. Thus, long-term stimulated human primary cultures demonstrate a clear relation with the tumor in vivo and could therefore be used as models for the disease.