Abstract
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.
| Original language | English |
|---|---|
| Article number | 160 |
| Journal | Molecular Cancer |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jun 30 2014 |
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Keywords
- AGR2
- Endoplasmic reticulum stress
- Migration and invasion
- Survival
- Thyroid cancer
ASJC Scopus subject areas
- Cancer Research
- Molecular Medicine
- Oncology
Cite this
Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells. / Di Maro, Gennaro; Salerno, Paolo; Unger, Kristian; Orlandella, Francesca M.; Monaco, Mario; Chiappetta, Gennaro; Thomas, Gerry; Oczko-Wojciechowska, Malgorzata; Masullo, Mariorosario; Jarzab, Barbara; Santoro, Massimo; Salvatore, Giuliana.
In: Molecular Cancer, Vol. 13, No. 1, 160, 30.06.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells
AU - Di Maro, Gennaro
AU - Salerno, Paolo
AU - Unger, Kristian
AU - Orlandella, Francesca M.
AU - Monaco, Mario
AU - Chiappetta, Gennaro
AU - Thomas, Gerry
AU - Oczko-Wojciechowska, Malgorzata
AU - Masullo, Mariorosario
AU - Jarzab, Barbara
AU - Santoro, Massimo
AU - Salvatore, Giuliana
PY - 2014/6/30
Y1 - 2014/6/30
N2 - 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.
AB - 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.
KW - AGR2
KW - Endoplasmic reticulum stress
KW - Migration and invasion
KW - Survival
KW - Thyroid cancer
UR - http://www.scopus.com/inward/record.url?scp=84903327168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903327168&partnerID=8YFLogxK
U2 - 10.1186/1476-4598-13-160
DO - 10.1186/1476-4598-13-160
M3 - Article
C2 - 24976026
AN - SCOPUS:84903327168
VL - 13
JO - Molecular Cancer
JF - Molecular Cancer
SN - 1476-4598
IS - 1
M1 - 160
ER -