Category: Basic Science: Oncology

MP1-8 - Enhanced Apurinic/Apyrimidinic Endonuclease Activity in Non-Muscle Invasive Bladder Cancer

Thu, Sep 20
4:00 PM - 6:00 PM

Introduction & Objective :

Base excision repair (BER)capacity of cancer cells protect themselves against DNA damaging therapeutic agents induced cell death, and thus decrease the efficacy of the anticancer therapy. Therefore, the enhanced BER capacity of cancer cells is disadvantageous to cancer treatment. A BER enzyme, apurinic/apyrimidinic endonuclease (APE1), repairs mutagenic and cytotoxic AP sites in DNA. APE1 is found to be overexpressed in multiple cancer types. The overexpression of APE1 is associated with resistance toi ncreased sensitivity to various anticancer drugs and ionizing radiation, and downregulation or suppression of APE1 function in different cancer types. However, BER capacity of non-muscle invasive bladder cancer(NMIBC) processes is not known. Therefore, the aim of this study was to determine whether APE1 function and BER capacity plays a role in progression of NMIBC.


Methods :

The APE1 activity was measured in whole tissue extracts of 17 NMBIC patientsand the corresponding normal tissues using a [γ-32P] ATP labeled 51-mer tetrahydrofuran-containing DNA substrate. During cystoscopy, the biopsy of the control tissue was taken from the normal appearing mucosa, which was sapled as far from the  aspossible to the tumor location as possible. cold cup biopsy sample was taken from the tumor. If multiple tumors were present, the largest lesion was sampled. The control sample was taken initially in order to prevent tumor spillage and contamination. Histological confirmation of the control samples were also made by routine pathological examination.  The percentage of incision was calculated as the amount of radioactivity present in the product band relative to the total radioactivity. APE1 protein levels were measured by western blot analysis. The differences were analyzed by the Student’s t-test.


Results : APE1 activity was significantly higher in all NMBIC tissues compared with corresponding normal tissues (p<0.0001). The activity was 2.11±0.12 fold higher in all NMIBC tissues than corresponding normal tissue. Furthermore, APE1 protein level was also higher in all NMBIC tissues than in the corresponding normal tissues.


Conclusions :

APE1 activity and protein level was significantly higher in bladder cancer tissue of patients with NMIBC, compared to their non-cancerous bladder tissue.

Mehmet Selçuk Keskin

Assist. Prof
Acibadem Mehmet Ali Aydınlar University School of Medicine Urology department
Istanbul, Istanbul, Turkey

Berna Somuncu

Acibadem Mehmet Ali Aydınlar University Faculty of Arts and Sciences Molecular Biology and Genetics
Istanbul, Istanbul, Turkey

Merve Antmen

ehmet Ali Aydınlar University Faculty of Arts and Sciences Molecular Biology and Genetics
Istanbul, Istanbul, Turkey

Yeşim Sağlıcan

Mehmet Ali Aydınlar University School of Medicine Pathology department
Istanbul, Istanbul, Turkey

Tuğçe Ertüzün

ehmet Ali Aydınlar University Faculty of Arts and Sciences Molecular Biology and Genetics
Istanbul, Istanbul, Turkey

Mustafa Bilal Tuna

MD
Acibadem Maslak Hospital, Department of Urology
Is, Istanbul, Turkey

Can Öbek

Prof.
Acibadem Taksim Hospital
Istanbul, Istanbul, Turkey

Ümit İnce

Mehmet Ali Aydınlar University School of Medicine Pathology department
Istanbul, Istanbul, Turkey

Ali Rıza Kural

Prof.
Acibadem Mehmet Ali Aydınlar University School of Medicine Urology department
Istanbul, Istanbul, Turkey

Meltem Müfütoğlu

ehmet Ali Aydınlar University Faculty of Arts and Sciences Molecular Biology and Genetics
Istanbul, Istanbul, Turkey