Conclusions
These data indicate that loss of Rap1GAP is a frequent event in PTC. The more frequent and greater down-regulation of Rap1GAP in PTCs compared with adenomas suggests a role for Rap1GAP depletion in the progression of human thyroid tumors, possibly through unrestrained Rap activity.
Methods
A highly specific Rap1GAP antibody was applied to sections of 55 human thyroid tissues. Genomic DNA was analyzed for the presence of the BRAF(V600E) mutation, and loss of Rap1GAP. Rap1GAP expression in rat thyroid cells was abolished using small interfering RNA.
Results
We observed that down-regulation of Rap1GAP in benign lesions and PTCs was common. Rap1GAP expression was more severely decreased in PTCs. Loss of Rap1GAP expression was observed in multiple histological variants of PTCs. Approximately 20% of PTCs and adenomas exhibited allelic loss of Rap1GAP. Loss of Rap1GAP was not associated with the presence of the BRAF(V600E) mutation. In vitro, loss of Rap1GAP was sufficient to increase Rap1 activity in thyroid cells. Conclusions: These data indicate that loss of Rap1GAP is a frequent event in PTC. The more frequent and greater down-regulation of Rap1GAP in PTCs compared with adenomas suggests a role for Rap1GAP depletion in the progression of human thyroid tumors, possibly through unrestrained Rap activity.