JQ1 suppresses tumor growth via PTEN/PI3K/AKT pathway in endometrial cancer

• DOI: 10.18632/oncotarget.11631
• Publication Date: 2016-08-26T19:48:48Z
• Authors: Haifeng Qiu; Jing Li; Leslie H. Clark; Amanda L. Jackson; Lu Zhang; Hui Guo; Joshua E. Kilgore; Paola A. Gehrig; Chunxiao Zhou; Victoria L. Bae-Jump
• Keywords: Gynecologic oncology

// Haifeng Qiu 1, 2 , Jing Li 3 Leslie H. Clark Amanda L. Jackson Lu Zhang 2, 4 Hui Guo Joshua E. Kilgore Paola A. Gehrig Chunxiao Zhou 5 Victoria Bae-Jump 1 Department of Obstetrics and Gynecology, the First Affiliated Hospital Zhengzhou University, Zhengzhou, China Division Gynecological Oncology, University North Carolina at Chapel Hill, NC, USA Gynecologic Shandong Cancer Institute, Jinan, Lineberger Center, Correspondence to: Bae-Jump, email: [e-mail] Zhou, [e-mail] Keywords: endometrial cancer, JQ1, BRD4 inhibitor, PTEN/PI3K/AKT signal pathway, intrinsic resistance Received: April 15, 2016 Accepted: August 10, Published: 26, ABSTRACT Overexpression c-Myc is associated with worse outcomes in indicating that may be a promising target for cancer therapy. A novel small molecule, has been shown to block resulting inhibition expression tumor growth. Thus, we investigated whether JQ1 can inhibit growth cell culture xenograft models. In PTEN-positive cells, significantly suppressed proliferation via induction G1 phase arrest apoptosis dose-dependent manner, accompanied by sharp decline cyclin D1 CDK4 protein expression. However, PTEN-negative cells exhibited despite significant inhibition. Moreover, found PTEN its downstream PI3K/AKT signaling targets were modulated as evidenced microarray analysis. Silencing resulted while upregulation increased sensitivity JQ1. xenografts models PTEN-knock-in upregulated PTEN, blocked pathway These effects attenuated PTEN-knockdown appears highly status cancer. Our findings suggest targeting using might serve therapeutic strategy cancers.