Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor  

作　　者：Seakwoo Lee Kevin K Desai Kenneth A Iczkowski Robert G Newcomer Kevin J WU Yun-Ge Zhao Winston W Tan Mark D Roycik Qing-Xiang Amy Sang 

机构地区：[1]Department of Chemistry and Biochemistry and lnstitute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA [2]Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Gainesville, FL 32608, USA [3]Department of Pathology, Immunology, and Laboratory of Medicine, University of Florida College of Medicine, GainesviIle, FL 32610, USA [4]Department of Pathology, Medicine, Mayo Clinic, Jacksonville, FL 32224, USA [5]Department of lnternal Medicine, Hematology/Oncology, Mayo Clinic, Jacksonville, FL 32224, USA

出　　处：《Cell Research》2006年第9期750-758,共9页细胞研究（英文版）

摘　　要：The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

关 键 词：matrix metalloproteinase-26 tissue inhibitor of metalloproteinases-4 high-grade prostatic intraepithel ialneoplasia prostate cancer biomarkers early diagnosis IMMUNOHISTOCHEMISTRY CO-IMMUNOPRECIPITATION 

分 类 号：R737.25[医药卫生—肿瘤]