NF-kappaB and COX-2 during oral tumorigenesis and in assessment of minimal residual disease in surgical margins.
Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significantly improved over the last few decades. Classical diagnostic methods are still not sensitive enough in detecting completeness of surgery and assessing minimal residual disease. This study investigated the role of NF-kappaB and COX-2 both in oral cancer progression and assessment of minimal residual disease. Expression of NF-kappaB proteins and its inhibitory protein IkappaB-alpha was evaluated using immunohistochemistry, ELISA and EMSA, while RT-PCR was used to detect COX-2 expression. Cytoplasmic expression as well as nuclear translocation of NF-kappaB proteins increased with histological progression of oral cancer (from normal to leukoplakia to cancer). A similar pattern of expression was observed for COX-2 also. NF-kappaB proteins, both cytoplasmic and nuclear, had a significant negative correlation from tumor to surgical margin to extra margin; COX-2 paralleled the expression of NF-kappaB proteins. Our results thus point to NF-kappaB and COX-2 as participants in oral tumor progression and also to the validation of these two molecular markers in assessing minimal residual disease.
Santhi
W S
WS
Department of Molecular Medicine, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
Sebastian
Paul
P
Varghese
Bipin T
BT
Prakash
Om
O
Pillai
M Radhakrishna
MR
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D016328:NF-kappa B / Q000378:metabolism*; D018365:Neoplasm, Residual / Q000175:diagnosis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human