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.
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.
Pacheco
Mercia Medeiros
MM
Fundação Oncocentro de São Paulo, Brazil.
Kowalski
Luis Paulo
LP
Nishimoto
Ines Nobuko
IN
Brentani
Maria Mitzi
MM
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
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