Manzar Alam1, Tanushree Kashyap1, Kamdeo K Pramanik1, Abhay K Singh1, Siddavaram Nagini2, Rajakishore Mishra3. 1. Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe Ranchi, Jharkhand, 835205, India. 2. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India. 3. Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe Ranchi, Jharkhand, 835205, India. rajakishore.mishra@cuj.ac.in.
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.
OBJECTIVES:Oral cancer is the sixth most common cancer in the world. Failure of chemoradiation therapy is a major concern for treating oral cancerpatients. 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 humantongue 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.
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Birgit Kreiseder; Yvonne M Holper-Schichl; Barbara Muellauer; Nico Jacobi; Alexander Pretsch; Johannes A Schmid; Rainer de Martin; Harald Hundsberger; Andreas Eger; Christoph Wiesner Journal: PLoS One Date: 2015-03-20 Impact factor: 3.240
Authors: Mircea Tampa; Madalina Irina Mitran; Cristina Iulia Mitran; Maria Isabela Sarbu; Clara Matei; Ilinca Nicolae; Ana Caruntu; Sandra Milena Tocut; Mircea Ioan Popa; Constantin Caruntu; Simona Roxana Georgescu Journal: J Immunol Res Date: 2018-11-12 Impact factor: 4.818