:: Volume 7, Issue 2 (Int J Mol Cell Med 2018) ::
Int J Mol Cell Med 2018, 7(2): 119-132 Back to browse issues page
Dysregulated Expression and Sub cellular Localization of Base Excision Repair (BER) Pathway Enzymes in Gallbladder Cancer
Manoj Kumar * 1, Vijay Kumar Shukla 2, Pravas Kumar Misra 3, Mercy Jacob Raman 4
1- Cytogenetics laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India., School of Biological and Environmental Sciences, Faculty of Basic Sciences, Shoolini University, Solan, Himachal Pradesh, India. , manoj@shooliniuniversity.com
2- Department of General Surgery, Institute of Medical Science, Banaras Hindu University, Varanasi, India.
3- Departments of Pathology and Surgery, Indian Railways Cancer Institute and Research Centre, Varanasi, Uttar Pradesh, India.
4- Cytogenetics laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.
Abstract:   (449 Views)
Base excision repair (BER) pathway is one of the repair systems that have an impact on the radiotherapy and chemotherapy for the cancer patients. The molecular pathogenesis of gallbladder cancer is not known extensively. In the present study we investigated whether the expression of AP endonuclease 1 (APE1) and DNA polymerase β (DNA pol β), key enzymes of BER pathway has any clinical significance with gallbladder carcinogenesis. 41 gallbladder cancer, 27 chronic cholecystitis, and 3 normal gallbladder specimens were analyzed for the expression of APE1 and DNA polymerase β by western blotting, and sub cellular localization were studied by immunohistochemistry. The enzymatic activity of APE1 was also studied. The correlations with expression of the above proteins with clinical-pathological characteristics of gallbladder cancer patients were analyzed. The integrated density value ratio (relative expression) of total APE1 (37 kDa + 35 kDa variant) analyzed in the three groups of tissues, were 0.76±0.03 in normal gallbladder, 0.91±0.08 in chronic cholecystitis, and 1.12±0.05 in gallbladder cancer. APE1 was found to be up-regulated in 80% of gallbladder carcinoma samples (P = 0.01). A positive trend of APE1 expression with tumor stage and lymph node positivity was observed. The enzymatic activity of APE1 was found higher in gallbladder cancer samples in comparison with chronic cholecystitis. The integrated density value  ratio of DNA polymerase β for normal gallbladder, chronic cholecystitis and gallbladder cancer tissue samples were 0.46±0.03, 0.7±0.06 and 1.33±0.1, respectively. DNA polymerase β was found to be up regulated in almost all gallbladder carcinoma samples (P = 0.0001), and its expression was negatively correlated with age (P = 0.02). DNA polymerase β expression showed a positive trend with tumor stage and nuclear differentiation of gallbladder cancer. . It may be concluded that alteration of these BER pathway proteins may be the causal factors for carcinogenesis of gallbladder, and has targeted therapeutic potential.
Keywords: AP endonuclease1, DNA polymerase β, chronic cholecystitis, gallbladder cancer.
Full-Text [PDF 1283 kb]   (80 Downloads)    
Type of Study: Original Article | Subject: Cancer
Received: 2018/06/17 | Accepted: 2018/08/14 | Published: 2018/08/18



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Volume 7, Issue 2 (Int J Mol Cell Med 2018) Back to browse issues page