| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Departments of Oto-Neuro-Ophthalmologic Surgery;* Experimental Pathology and Oncology; Pediatrics, Onco-Haematology Unit; Human Pathology and Oncology; and Preclinical and Clinical Pharmacology,¶ University of Florence, Florence, Italy
The goal of this study was to analyze the correlation between inducible nitric oxide synthase (iNOS) and COX-2 activities and p53 gene status in head and neck squamous cell carcinomas (HNSCCs) in vivo and in vitro. In a series of 43 HNSCCs we observed an up-regulation of both iNOS and COX-2 pathways in tumor tissues and both activities were correlated each other (rs = 0.612 and P = 0.0002). We also found that p53-mutated HNSCCs (25 cases, 58.1%) showed higher levels of iNOS activity and cGMP in comparison with wild-type p53 tumors (18 cases, 41.9%) (P = 0.0005 and P = 0.01), as well as higher iNOS immunohistochemical expression (P = 0.03). Analogously, higher PgE2 levels were documented in p53-mutated HNSCCs when compared with wild-type p53 tumors (P = 0.015) and COX-2 protein expression was higher in p53-mutated HNSCCs (P = 0.007). A431 cancer cells expressing a p53 temperature-sensitive mutant showed an 
1.9- and 2.6-fold decrease in spontaneous NO2-/NO3- and PgE2 synthesis at permissive temperature, respectively, when compared with the same cells at nonpermissive temperature (P 
0.001). Basal levels of iNOS and COX-2 proteins and mRNAs were markedly suppressed by restoration of p53 activity. Our results indicate that p53 gene mutation(s) may be responsible for iNOS and COX-2 up-regulation frequently observed in HNSCCs and suggest that restoration of wild-type p53 expression may interfere with tumor growth by inhibiting iNOS and COX-2 pathways.
This article has been cited by other articles:
 |
|
 |
|
  K. M. Rassnick and B. L. Njaa Cyclooxygenase-2 immunoreactivity in equine ocular squamous-cell carcinoma J Vet Diagn Invest, July 1, 2007; 19(4): 436 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Marwaha, Y.-H. Chen, E. Helms, S. Arad, H. Inoue, E. Bord, R. Kishore, R. D. Sarkissian, B. A. Gilchrest, and D. A. Goukassian T-oligo Treatment Decreases Constitutive and UVB-induced COX-2 Levels through p53- and NF{kappa}B-dependent Repression of the COX-2 Promoter J. Biol. Chem., September 16, 2005; 280(37): 32379 - 32388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D. Gross, J. O. Boyle, J. D. Morrow, M. K. Williams, C. S. Moskowitz, K. Subbaramaiah, A. J. Dannenberg, and A. J. Duffield-Lillico Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers Clin. Cancer Res., August 15, 2005; 11(16): 6087 - 6093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Jeon, S. Kang, D.-H. Kang, K.-Y. Yoo, I.-A. Park, Y.-J. Bang, J. W. Kim, N.-H. Park, S.-B. Kang, H.-P. Lee, et al. Cyclooxygenase-2 and p53 Expressions in Endometrial Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1538 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishimura, S. F. Bronk, and G. J. Gores Inducible nitric oxide synthase upregulates cyclooxygenase-2 in mouse cholangiocytes promoting cell growth Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G88 - G95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-L. Erkinheimo, H. Lassus, P. Finne, B. P. van Rees, A. Leminen, O. Ylikorkala, C. Haglund, R. Butzow, and A. Ristimaki Elevated Cyclooxygenase-2 Expression Is Associated with Altered Expression of p53 and SMAD4, Amplification of HER-2/neu, and Poor Outcome in Serous Ovarian Carcinoma Clin. Cancer Res., January 15, 2004; 10(2): 538 - 545. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
