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KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.
Qiu, Mei-Ting; Fan, Qiong; Zhu, Zhu; Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C; Wong, Kwong-Kwok; Bao, Wei.
Affiliation
  • Qiu MT; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Fan Q; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhu Z; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kwan SY; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Chen L; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Chen JH; Departments of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, TongJi University School of Medicine, Shanghai, China.
  • Ying ZL; Department of Dermatology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhou Y; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Gu W; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang LH; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Cheng WW; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zeng J; Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wan XP; Departments of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, TongJi University School of Medicine, Shanghai, China.
  • Mok SC; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wong KK; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bao W; Departments of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Oncotarget ; 6(31): 31702-20, 2015 Oct 13.
Article in En | MEDLINE | ID: mdl-26397136
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.
Subject(s)
Key words

Full text: 1 Database: MEDLINE Main subject: Receptors, Androgen / Gene Expression Regulation, Neoplastic / Proto-Oncogene Proteins c-myc / Endometrial Neoplasms / Cyclin-Dependent Kinase Inhibitor p27 / Jumonji Domain-Containing Histone Demethylases Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Language: En Year: 2015 Type: Article

Full text: 1 Database: MEDLINE Main subject: Receptors, Androgen / Gene Expression Regulation, Neoplastic / Proto-Oncogene Proteins c-myc / Endometrial Neoplasms / Cyclin-Dependent Kinase Inhibitor p27 / Jumonji Domain-Containing Histone Demethylases Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Language: En Year: 2015 Type: Article