title: Up-regulation of urinary-type plasminogen activator correlates with high-risk papillary thyroid carcinoma with BRAF(V600E) mutation and its possible molecular mechanism.
abstract: The aim of the present study is to investigate the relationship between urinary-type plasminogen activator (uPA) expression and clinicopathological features in papillary thyroid carcinoma (PTC) and to determine the signal transduction of PTC cells in vitro. PTC tissues from 42 patients were analyzed for the expression of uPA and the BRAF(V600E) mutation. BCPAP, a PTC cell line harboring the BRAF(V600E) mutation, was used to study MAPK signaling. PCR and direct sequencing were applied to analyze BRAF(V600E) mutation status. uPA mRNA expression was measured using a quantitative RT-PCR method, and uPA protein was localized using an immunohistochemical method. The ERK protein status was detected by Western blot analysis. uPA gene expression was significantly increased in PTC tissues as compared to the corresponding non-tumor tissues. Furthermore, the up-regulation of uPA mRNAs was correlated with high-risk clinicopathological features, including extrathyroid invasion, loss of cellular polarity/cohesiveness, and the BRAF(V600E) mutation. Marked dephosphorylation of ERK1/2 and down-regulation of uPA expression were detected when BCPAP was treated with a MEK inhibitor, U0126. MEK inhibitors might be a potential treatment strategy for aggressive PTC with BRAF(V600E) through inhibition of uPA expression.
authors.affiliation: Department of Pathology and Laboratory Medicine, Hara Hospital, Kinki University School of Medicine, 1248-1, Otoda, Ikoma, Nara 630-0293, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Wakasa
authors.affiliation: Department of Pathology, Taishan Medical University, 2# Yingsheng Dong Road, Tai'an City, Shandong 271000, PR China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, PR China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pathology and Pathophysiology, Shandong University School of Medicine, Shandong 250012, PR China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Social Insurance Kinan Hospital, 46-70 Shinjo-cho, Tanabe, Wakayama 646-858, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Pathology, International University of Health and Welfare Mita Hospital, 143 Mita, Minato-ku, Tokyo 108-8329, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.affiliation: Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe 650-0011, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.affiliation: Department of Medical Technology, Tokiwa University, 2-6-2 Ootani, Nagata-ku, Kobe 653-0838, Japan.
authors.forename: Kennichi
authors.initials: K
authors.lastname: Kakudo
authors.affiliation: Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, 158, Mizuma, Kaizuka-City, Osaka 597-0104, Japan. Electronic address: nakamuram@kawasakigakuen.ac.jp.
authors.forename: Misa
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D002070:Butadienes / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014568:Urokinase-Type Plasminogen Activator
keywords: BRAF; ERK1/2; MEK inhibitor; Papillary thyroid cancer; Urinary-type plasminogen activator