title: Low TWEAK expression is correlated to the progression of squamous cervical carcinoma.
abstract: OBJECTIVE
  To investigate the correlation of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its specific receptor fibroblast growth factor-inducible immediate-early response protein 14 (Fn14) to cervical carcinogenesis by examining TWEAK/Fn14 expression levels or locations in different cervical tissues and cells.
  
  
  METHODS
  TWEAK/Fn14 mRNA expressions were detected by quantitative real-time PCR in total of 120 cervical samples including normal, precancerous and cancerous tissues, while protein expressions were detected by immunofluorescent staining and western blot in both tissues and cell lines. Correlation between TWEAK expression levels to cancer progression and clinicopathologic features was statistically analyzed.
  
  
  RESULTS
  The TWEAK expression was significantly decreased while Fn14 expression was increased in carcinoma and cervical intraepithelial neoplasm (CIN) specimens compared with that in normal control specimens. A similar trend of TWEAK/Fn14 expression was also observed in cervical cell lines. In addition, TWEAK expression decreased further along with the interstitial depth of invasion (P<0.05) and tumor grade (P<0.05), suggesting that TWEAK acts rather on local cancer tissue infiltration.
  
  
  CONCLUSIONS
  TWEAK/Fn14 pathway may play a role in the development of squamous cervical carcinoma, in which the reduced level of TWEAK could promote the progression and invasion of cervical cancer. An increase in Fn14 may reflect a compensatory response to decreased TWEAK and may provide a novel therapeutic target for human cervical cancer treatment or a biomarker for cervical cancer diagnosis.
authors.affiliation: Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, Chengdu, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zou
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gan
authors.forename: Long
authors.initials: L
authors.lastname: Jiang
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000074049:Cytokine TWEAK; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000074049:Cytokine TWEAK; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors