title: Urokinase-type plasminogen activator resulting from endometrial carcinogenesis enhances tumor invasion and correlates with poor outcome of endometrial carcinoma patients.
abstract: The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC.
authors.affiliation: 1] Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan [2] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsin-Chu, Taiwan.
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Tang
authors.affiliation: Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsin-Chu, Taiwan.
authors.forename: Hsien-Da
authors.initials: HD
authors.lastname: Huang
authors.affiliation: Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.affiliation: 1] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsin-Chu, Taiwan [3] Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C479138:PLOD2 protein, human; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator