Oncotarget

Research Papers:

KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

Mei-Ting Qiu, Qiong Fan, Zhu Zhu, Suet-Ying Kwan, Limo Chen, Jin-Hong Chen, Zuo-Lin Ying, Ye Zhou, Wei Gu, Li-Hua Wang, Wei-Wei Cheng, Jianfang Zeng, Xiao-Ping Wan, Samuel C. Mok, Kwong-Kwok Wong and Wei Bao _

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Oncotarget. 2015; 6:31702-31720. https://doi.org/10.18632/oncotarget.5165

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Abstract

Mei-Ting Qiu1,*, Qiong Fan1,*, Zhu Zhu2,*, Suet-Ying Kwan2, Limo Chen3, Jin-Hong Chen4, Zuo-Lin Ying5, Ye Zhou1, Wei Gu1, Li-Hua Wang1, Wei-Wei Cheng1, Jianfang Zeng6, Xiao-Ping Wan4, Samuel C. Mok2, Kwong-Kwok Wong2, Wei Bao1,2

1Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China

2Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

4Departments of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, TongJi University School of Medicine, Shanghai, China

5Department of Dermatology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

6Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

*These authors have contributed equally to this work

Correspondence to:

Wei Bao, e-mail: forever_chipper@hotmail.com

Keywords: endometrial cancer, lysine demethylases KDM4B and KDM4A, androgen receptor, histone modification, c-myc, p27kip1, prognosis

Received: May 21, 2015     Accepted: August 29, 2015     Published: September 11, 2015

ABSTRACT

Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity.


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