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Clinical Oral Investigations

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01-12-2017 | Original Article

The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance

Authors: Manzar Alam, Tanushree Kashyap, Kamdeo K. Pramanik, Abhay K. Singh, Siddavaram Nagini, Rajakishore Mishra

Published in: Clinical Oral Investigations | Issue 9/2017

Abstract

Objectives

Oral cancer is the sixth most common cancer in the world. Failure of chemoradiation therapy is a major concern for treating oral cancer patients. The objective of this study is to determine the B cell lymphoma-2 (bcl-2) expression and its regulation by nuclear factor κB (NFκB) and activator protein 1 (AP-1) in oral cancer progression and chemoradiation resistance.

Materials and methods

In the present study, a total of 123 (n = 123) human samples were included. Briefly, 64 fresh samples were from adjacent normal (AN), primary oral tumors without treatment (PT), and tumors with resistance to chemoradiation therapy with local recurrence (RCRT). Fifty-nine samples were human tongue cancers and normal samples (TMA). Messenger RNA (mRNA) expression levels of bcl-2 and protein levels of bcl-2, NFκB, AP-1, and inactive GSK3α/β were measured by semiquantitative RT-PCR, immunohistochemistry, Western blot, and ChIP analysis.

Results

Increased bcl-2 expression was observed in PT compared to AN. The RCRT tumors showed maximum expression of bcl-2 mRNA and protein over the PT and AN groups. Bcl-2 protein and mRNA expression were positively correlated with NFκB and AP-1 expression. AP-1 expression was strongly correlated with bcl-2 in the RCRT group of tumors. Further, inactive GSK3α/β showed a positive trend with bcl-2 expression in oral tongue cancer specimens.

Conclusion

Collectively, our results demonstrated cumulative effect of AP-1 and NFĸB for bcl-2 gene regulation in overall PT progression and chemoradiation resistance. The study provides evidence of increased bcl-2 mRNA/protein fueled by NFĸB in PT and AP-1 in RCRT. These regulations of bcl-2 by NFκB and AP-1 are important in OSCC progression and chemoradiation resistance.

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Title: The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance
Authors: Manzar Alam
Tanushree Kashyap
Kamdeo K. Pramanik
Abhay K. Singh
Siddavaram Nagini
Rajakishore Mishra
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 9/2017
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-017-2074-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance

Abstract

Objectives

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusion

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