title: Differential expression of c-jun and c-fos mRNAs in squamous cell carcinoma of the head and neck: associations with uPA, gelatinase B, and matrilysin mRNAs.
abstract: BACKGROUND
  Head and neck squamous cell carcinomas (HNSCC) are known for their invasive behavior. The invasiveness of these tumors requires proteases, some of which as urokinase-type plasminogen activator (uPA), gelatinase B and matrilysin are regulated through AP-1 dependent transcriptional mechanisms. AP-1 consists of several proteins, including those encoded by the proto-oncogenes c-jun and c-fos. The aim of this study was to: first, evaluate the expression levels of matrix metalloproteases (matrilysin and gelatinase B) and uPA mRNAs; second, examine whether these genes might be associated with c-jun and c-fos expression; third, examine the relationship between the expression of these genes and HNSCC clinico-pathological features.
  
  
  METHODS
  We have analyzed 38 HNSCC primary tumors and matched mucosa tissues for uPA, gelatinase B, matrilysin, c-fos, and c-jun by Northern-blot analysis.
  
  
  RESULTS
  uPA, gelatinase B, matrilysin, and c-jun mean levels were statistically higher in the tumors than in the normal adjacent mucosa, whereas no difference was found when c-fos mRNA values were compared, c-jun mRNA expression correlated directly with gelatinase B and matrilysin mRNA levels, but no association with uPA mRNA was observed, c-fos mRNA levels were not associated with the tested proteases, but low levels were determined in tumors from older patients who subsequently developed a 2(nd) tumor. No evidence of correlation between expression of uPA, matrilysin, and c-jun in tumors and clinico-pathological features was found. Gelatinase B mRNA high levels were associated to presence of cervical recurrences.
  
  
  CONCLUSIONS
  Expression of c-jun seems to be involved in the regulation of gelatinase B and matrilysin being not related to uPA. Lack of association with c-fos may indicate that other fos family members might play a role in the transcriptional activity of the analyzed proteases in HNSCC tumors.
authors.affiliation: Fundação Oncocentro de São Paulo, Brazil.
authors.forename: Mercia Medeiros
authors.initials: MM
authors.lastname: Pacheco
authors.forename: Luis Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.forename: Ines Nobuko
authors.initials: IN
authors.lastname: Nishimoto
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D046508:Culture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014568:Urokinase-Type Plasminogen Activator; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9