Upregulation of minichromosome maintenance complex component 3 during epithelial-to-mesenchymal transition in human prostate cancer

Abstract

// Paul A. Stewart 1, * , Zahraa I. Khamis 1, 4, * , Haiyen E. Zhau 2, * , Peng Duan 2 , Quanlin Li 2 , Leland W.K. Chung 2 and Qing-Xiang Amy Sang 1, 3 1 Department of Chemistry & Biochemistry, Florida State University, Tallahassee, FL, United States of America 2 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America 3 Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, United States of America 4 Laboratory of Cancer Biology and Molecular Immunology, Department of Biochemistry, Faculty of Sciences, Lebanese University, Beirut, Lebanon * These authors have contributed equally to this work Correspondence to: Qing-Xiang Amy Sang, email: qxsang@chem.fsu.edu Haiyen E. Zhau, email: haiyen.zhau@cshs.org Keywords: epithelial-to-mesenchymal transition, minichromosome maintenance complex proteins, metastasis, androgen receptor, proteomics Received: September 06, 2016      Accepted: March 08, 2017      Published: April 05, 2017 ABSTRACT Metastasis is often associated with epithelial-to-mesenchymal transition (EMT). To understand the molecular mechanisms of this process, we conducted proteomic analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental model of metastatic human prostate cancer. The protein signatures of epithelial (ARCaP E ) and mesenchymal (ARCaP M ) cells were consistent with their phenotypes. Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a crucial subunit of DNA helicase, was significantly higher in ARCaP M cells than that of ARCaP E cells. This increased MCM3 protein expression level was verified using Western blot analysis of the ARCaP cell lineages. Furthermore, immunohistochemical analysis of MCM3 protein levels in human prostate tissue specimens showed elevated expression in bone metastasis and advanced human prostate cancer tissue samples. Subcutaneous injection experiments using ARCaP E and ARCaP M cells in a mouse model also revealed increased MCM3 protein levels in mesenchymal-derived tumors. This study identifies MCM3 as an upregulated molecule in mesenchymal phenotype of human prostate cancer cells and advanced human prostate cancer specimens, suggesting MCM3 may be a new potential drug target for prostate cancer treatment.