Loss of MED12 Induces Tumor Dormancy in Human Epithelial Ovarian Cancer via Downregulation of EGFR

A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator o...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13), p.3532-3543
Main Authors: Luo, Xiao-Lin, Deng, Cheng-Cheng, Su, Xiao-Dong, Wang, Fang, Chen, Zhen, Wu, Xing-Ping, Liang, Shao-Bo, Liu, Ji-Hong, Fu, Li-Wu
Format: Article
Language:English
Subjects:
Cell proliferation
Chemotherapy
DNA microarrays
DNA-directed RNA polymerase
Dormancy
Epidermal growth factor receptors
Molecular chains
Ovarian cancer
Ovarian carcinoma
RNA polymerase II
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells and , and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation. Additionally, MED12 bound to the promoter of EGFR, and correlation studies showed that MED12 expression positively correlated with EGFR expression in EOC patient samples. Clinical data demonstrated that chemotherapy-resistant patients expressed lower levels of MED12 compared with responsive patients. Overall, our data show that MED12 plays an important role in regulating dormancy of EOC through regulation of EGFR. MED12 is identified as a novel, important regulator of tumor dormancy in human ovarian cancer. .
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-18-0134