TY - JOUR
T1 - Inhibition of enhancer of zeste homolog 2 (ezh2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines
AU - Eskander, Ramez N.
AU - Ji, Tao
AU - Huynh, Be
AU - Wardeh, Rooba
AU - Randall, Leslie M.
AU - Hoang, Bang
PY - 2013/7
Y1 - 2013/7
N2 - Objective: To investigate the impact of enhancer of zeste homolog 2 (EZH2) expression on endometrial cancer cell line behavior. Materials and Methods: Enhancer of zeste homolog 2 expression levels were compared between the nonmalignant endometrial cell line T-HESC and 3 endometrial cancer cell lines, ECC-1, RL95-2, and HEC1-A. Stable EZH2 knockdown cell lines were created, and the impact on cellular proliferation, migration, and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. Enhancer of zeste homolog 2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and short-hairpin EZH2 cell lines was performed using the Student t test and the Fischer exact test. Results: Enhancer of zeste homolog 2 protein expression was increased in all 3 cancer cell lines and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration, and invasion. Down-regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in the G2/M phase. RNA interference of EZH2 expressionwas associatedwith an increase in the expression ofWnt pathway inhibitors sFRP1 and DKK3 and a concomitant decrease in A-catenin. Enhancer of zeste homolog 2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion, and nodal metastasis. Conclusions: Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation, migration, and invasion in 3 endometrial cancer cell lines as well as with increased stage, grade, depth of invasion, and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.
AB - Objective: To investigate the impact of enhancer of zeste homolog 2 (EZH2) expression on endometrial cancer cell line behavior. Materials and Methods: Enhancer of zeste homolog 2 expression levels were compared between the nonmalignant endometrial cell line T-HESC and 3 endometrial cancer cell lines, ECC-1, RL95-2, and HEC1-A. Stable EZH2 knockdown cell lines were created, and the impact on cellular proliferation, migration, and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. Enhancer of zeste homolog 2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and short-hairpin EZH2 cell lines was performed using the Student t test and the Fischer exact test. Results: Enhancer of zeste homolog 2 protein expression was increased in all 3 cancer cell lines and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration, and invasion. Down-regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in the G2/M phase. RNA interference of EZH2 expressionwas associatedwith an increase in the expression ofWnt pathway inhibitors sFRP1 and DKK3 and a concomitant decrease in A-catenin. Enhancer of zeste homolog 2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion, and nodal metastasis. Conclusions: Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation, migration, and invasion in 3 endometrial cancer cell lines as well as with increased stage, grade, depth of invasion, and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.
KW - EZH2
KW - Endometrial cancer
KW - Invasion
KW - Migration
KW - Pathology
KW - Uterine cancer
UR - http://www.scopus.com/inward/record.url?scp=84880279049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880279049&partnerID=8YFLogxK
U2 - 10.1097/IGC.0b013e318296a265
DO - 10.1097/IGC.0b013e318296a265
M3 - Article
C2 - 23792601
AN - SCOPUS:84880279049
SN - 1048-891X
VL - 23
SP - 997
EP - 1005
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 6
ER -