دورية أكاديمية
Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer
| العنوان: | Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer |
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| المؤلفون: | Tan, Xiaohui, Wang, Hongyi, Luo, Guangbin, Ren, Shuyang, Li, Wenmei, Cui, Jiantao, Gill, Harindarpal S., Fu, Sidney W., Lu, Youyong |
| المساهمون: | Fu, SW (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20037 USA., Minist Educ, Key Lab Carcinogenesis & Translat Res, Mol Oncol Lab, Beijing, Peoples R China., Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Dept Sugary, Beijing 100142, Peoples R China., Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA., George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20037 USA. |
| المصدر: | PubMed ; SCI |
| بيانات النشر: | international journal of biological sciences |
| سنة النشر: | 2015 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | DNA polymerase beta (POLB), gastric cancer, DNA Repair, point mutation, chemotherapy, BASE EXCISION-REPAIR, NEGATIVE BREAST-CANCER, COLORECTAL-CANCER, MURINE MELANOMA, CELL-LINES, DEFICIENCY, OVEREXPRESSION, CARCINOMAS, THERAPY, VARIANT |
| الوصف: | Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with-the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC. ; Biochemistry & Molecular Biology ; Biology ; SCI(E) ... |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1449-2288 |
| العلاقة: | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES.2015,11,(2),144-155.; 651173; http://hdl.handle.net/20.500.11897/341705Test; WOS:000350408200003 |
| DOI: | 10.7150/ijbs.10692 |
| الإتاحة: | https://doi.org/20.500.11897/341705Test https://doi.org/10.7150/ijbs.10692Test https://hdl.handle.net/20.500.11897/341705Test |
| رقم الانضمام: | edsbas.C96D53FC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14492288 |
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| DOI: | 10.7150/ijbs.10692 |