CHD1L promotes cell cycle progression and cell motility by up-regulating MDM2 in breast cancer

American Journal of Translational Research

Wei Wang¹  Jiayi Wu² 

[1] Comprehensive Breast Health Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, P. R. China;Pathology Department, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, P. R. China

关键词: Breast neoplasm;    CHD1L;    gene regulation;    MDM2;    tumor progression;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Chromodomain helicase/ATPase DNA-binding protein 1-like (CHD1L) gene is a novel oncogene amplified in many solid tumors. We investigated its role in breast cancer. CHD1L was over-expressed in 49.1% (57/116) breast cancer patients. Overexpression of CHD1L was significantly associated with younger age at diagnosis (P = 0.016), lymph node involvement (P = 0.040), higher tumor grade (P = 0.027), higher proliferation rate (P = 0.007) and shorter disease-free survival rate (77.2% vs. 91.5%, P = 0.037). A cDNA microarray analysis identified MDM2 as an important downstream target of CHD1L. And MDM2/p53 signaling pathway was showed to be significantly modulated by CHD1L. Further in vitro study showed that overexpression of CHD1L can promote tumorigenesis, metastasis, invasion and cell cycle progress. In vivo study confirmed the tumorigenesis ability of CHD1L. shRNA-mediated CHD1L silencing could abolishes the tumor-promotion effect of CHD1L in vitro and in vivo. In conclusion, CHD1L may promote the progress of breast cancer cells via the MDM2/p53 signaling pathway. This study identified CHD1L as a prognostic factor for breast cancer and MDM2 might be used as a potential target for therapeutic intervention in CHD1L overexpression breast cancer.

【 授权许可】

CC BY-NC