Background: Through a transcriptome microarray analysis, we have isolated Anterior gradient protein 2 (AGR2) as a
gene up-regulated in papillary thyroid carcinoma (PTC). AGR2 is a disulfide isomerase over-expressed in several
human carcinomas and recently linked to endoplasmic reticulum (ER) stress. Here, we analyzed the expression of
AGR2 in PTC and its functional role.
Methods: Expression of AGR2 was studied by immunohistochemistry and real time PCR in normal thyroids
and in PTC samples. The function of AGR2 was studied by knockdown in PTC cells and by ectopic expression
in non-transformed thyroid cells. The role of AGR2 in the ER stress was analyzed upon treatment of cells,
expressing or not AGR2, with Bortezomib and analyzing by Western blot the expression levels of GADD153.
Results: PTC over-expressed AGR2 at mRNA and protein levels. Knockdown of AGR2 in PTC cells induced
apoptosis and decreased migration and invasion. Ectopic expression of AGR2 in non-transformed human thyroid cells
increased migration and invasion and protected cells from ER stress induced by Bortezomib.
Conclusions: AGR2 is a novel marker of PTC and plays a role in thyroid cancer cell survival, migration, invasion and
protection from ER stress.