Autoimmune response to PARP and BRCA1/BRCA2 in cancer
نویسندگان
چکیده
PURPOSE To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer. METHODS Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer. RESULTS Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P < 0.001 and P < 0.01). Immunohistochemistry indicated that Pathology Grade at diagnosis to PARP1 expression in breast cancer was different (P < 0.05). CONCLUSIONS Different cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers.
منابع مشابه
بررسی موتاسیون های شایع ژن BRCA1 و BRCA2 در دختران مادران مبتلا به سرطان سینه و مقایسه آن با گروه کنترل
Background and purpose: Breast Cancer is one of the health problems in every population. The aim of this study was to determine the frequency of BRCA1 and BRCA2 common mutations in women whose mothers were diagnosed with breast cancer. Materials and methods: A case–control study was performed in 109 females (less than 40 years of age) who had mothers with breast cancer. For scanning of...
متن کاملThe Inhibition and Treatment of Breast Cancer with Poly (ADP-ribose) Polymerase (PARP-1) Inhibitors
BRCA1 and BRCA2 mutations are responsible for most familial breast carcinomas. Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity. Although these studies bring hope for BRCA muta...
متن کاملIN SILICO INVESTIGATION OF THE EFFECT OF LYCOPENE ON THE EXPRESSION OF BRCA1 AND BRCA2 INHIBITOR GENES IN PROSTATE CANCER
Background & Aims: Cancer is a genetic disease that results from mutations in genes that control cell activities. Prostate cancer is one of the most common types of cancers in men. Surgery, radiation therapy, hormone therapy, and chemotherapy are used to treat this disease. These treatments have numerous side effects after treatment, including impotence along with the high cost of treatment. In...
متن کاملThe PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells.
PARP inhibitors are considered promising anticancer agents and currently being tested in clinical trials in hereditary breast cancer patients harboring mutations in BRCA1 and BRCA2 genes. In this study, we investigated the antiproliferative effects and mechanism of PARP inhibitors ABT-888 (Veliparib), BSI-201 (Iniparib) and AZD228 (Olaparib) in breast cancer cell lines with BRCA1 or BRCA2 mutat...
متن کاملجهش های ژنتیکی جدید در ژن های اصلی سرطان پستان (BRCA1/BRCA2) در زنان ایرانی مبتلا به سرطان پستان زودرس
Background: Breast cancer is the most common female malignancy and the main cause of death in mid-aged women. Genetic germ line mutations in BRCAI/BRCA2 in Iranian women with breast or ovarian cancer have not been yet reported. Materials and methods: Clinical data, family history and blood samples were obtained from 83 females aged less than 45 years with primary breast cancer in order to su...
متن کامل