High NF-κB and STAT3 activity in human urothelial carcinoma: a pilot study.
OBJECTIVE
Given that the tumor-promoting inflammation has been previously established in squamous cell carcinoma of the bladder but its contribution to development of urothelial carcinoma (UC) still remains elusive, our aim was to study changes in expression and activity of inflammation-mediating NF-κB and STAT3 transcription factors in human urothelial bladder carcinoma as well as expression of their target genes cyclin D1, VEGFA and TGFβ1.


METHODS
Gene expression of STAT3, NF-κB, TGFβ1, cyclin D1 and VEGFA was measured by quantitative real-time polymerase chain reaction in both tumor and healthy bladder tissue from 36 patients with UC of the bladder. Activation of STAT3 and NF-κB was assessed with immunohistochemistry and immunoblot.


RESULTS
Urothelial bladder carcinoma displayed elevated expression as well as activation of NF-κB (P = 5.38e-10) and STAT3 (P = 0.002) transcription factors. Furthermore, elevated level of expression was observed for cyclin D1, VEGFA and TGFβ1 (P = 9.71e-09, P = 9.71e-09, P = 5.38e-10). Preliminary statistical analysis indicated that the level of upregulation of STAT3 or NF-κB was probably not dependent upon the grade (P = 0.984 and 0.803, respectively) and invasiveness of the tumor (0.399 and 0.949), nor to the gender (0.780 and 0.536) and age (0.660 and 0.816) of the patients.


CONCLUSIONS
NF-κB and STAT3 signaling pathways, as main inflammatory mediators, are found to be activated in urothelial bladder carcinoma indicating that chronic inflammatory processes are accompanying development of this tumor type. Future studies will have to determine possible causative role of inflammatory processes in development of urothelial bladder carcinomas.
Department of Immunology, School of Medicine, University of Split, Šoltanska 2, 21000, Split, Croatia.
Marina
M
Degoricija
Marijan
M
Situm
Jelena
J
Korać
Ana
A
Miljković
Katarina
K
Matić
Martina
M
Paradžik
Ivana
I
Marinović Terzić
Ana
A
Jerončić
Snježana
S
Tomić
Janoš
J
Terzić
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1