Authors: Weihua Li, Yanhong Tai, Jie Zhou, Weiting Gu, Zhaofang Bai, Tao Zhou, Zhijiu Zhong, Peter A. McCue, Nianli Sang, Jun-Yuan Ji, Beihua Kong, Jie Jiang and Chenguang Wang

Weihua Li

Department of Obstetrics and Gynecology; Qilu Hospital; Shandong University; Jinan, Shandong, China; Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA
These authors contributed equally to this work.

Yanhong Tai

Departments of Pathology; The 90th Hospital of Jinan; Jinan, Shandong, China
These authors contributed equally to this work.

Jie Zhou

Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA; Department of Endocrinology and Metabolism; Xijing Hospital; The Fourth Military Medical University; Xi'an, China
These authors contributed equally to this work.

Weiting Gu

Department of Obstetrics and Gynecology; Qilu Hospital; Shandong University; Jinan, Shandong, China; Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

Zhaofang Bai

Institute of Basic Medical Sciences; National Center of Biomedical Analysis; Beijing, China

Tao Zhou

Institute of Basic Medical Sciences; National Center of Biomedical Analysis; Beijing, China

Zhijiu Zhong

Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

Peter A. McCue

Department of Pathology; Thomas Jefferson University Hospital; Philadelphia, PA USA

Nianli Sang

Department of Biology and Graduate Program of Biological Sciences; College of Arts & Sciences; Drexel University; Philadelphia, PA USA

Jun-Yuan Ji

Department of Molecular and Cellular Medicine; College of Medicine; Texas A&M Health Science Center; College Station, TX USA

Beihua Kong

Department of Obstetrics and Gynecology; Qilu Hospital; Shandong University; Jinan, Shandong, China

Jie Jiang

Corresponding author: qljiangjie@sdu.edu.cn
Department of Obstetrics and Gynecology; Qilu Hospital; Shandong University; Jinan, Shandong, China

Chenguang Wang

Corresponding author: chenguang.wang@jefferson.edu
Department of Obstetrics and Gynecology; Qilu Hospital; Shandong University; Jinan, Shandong, China; Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

Abstract:
The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers.

Received: May 15, 2012; Accepted: May 20, 2012

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