摘要
目的 :进一步了解乳癌易感基因BRCA1与FHL2相互作用对FHL2转录激活功能的影响 ,为揭示BRCA1在肿瘤发生发展中的作用提供依据。方法 :将BRCA1C端缺失突变体BRCA1(△ 14 4 3～ 186 3aa)和BRCA1(△ 90 8～ 186 3aa)按正确读框插入到pCR3载体中 ,并在 2 93T细胞中表达。利用GAL4荧光素酶报告基因检测野生型BRCA1以及肿瘤易感突变体BRCA1(P174 9R) ,BRCA1(Y185 3insA) ,BRCA1(△ 14 4 3～ 186 3aa)和BRCA1(△ 90 8～ 186 3aa)对FHL2转录激活活性的调节作用。结果 :野生型BRCA1能增强FHL2转录激活活性 ,且具有剂量依赖性。而 4种肿瘤易感突变体增强FHL2转录激活活性的能力明显减弱。结论 :BRCA1与FHL2相互作用可能对基因转录调节以及肿瘤发生、发展中起着重要作用。
Objective:To further investigate the role of the BRCA1-FHL2 interaction in transcriptional regulation. Methods: Two tumor-derived C-terminal truncated mutants of breast cancer susceptibility gene 1(BRCA1),BRCA1(△1443-1863 aa)and BRCA1(△908-1863 aa), were made by inserting the corresponding cDNAs into the pCR3 vector, and expressed in 293T cells. The effect of BRCA1 and its mutants\[ BRCA1(P1749R),BRCA1(Y1853insA),BRCA1(△1443-1863 aa)and BRCA1(△908-1863 aa)\] on FHL2-mediated transcriptional activity was determined using a GAL4-luciferase reporter gene. Results:The wild type BRCA1 enhanced FHL2-mediated transcriptional activity in transient transfections in dose-dependent manner. All of the tumor-derived mutants had a reduced ability to enhance transactivation by FHL2. Conclusion:The BRCA1-FHL2 interaction may be involved in transcriptional regulation and play an important role in cancer growth.
出处
《军事医学科学院院刊》
CAS
CSCD
北大核心
2004年第6期519-522,共4页
Bulletin of the Academy of Military Medical Sciences
基金
国家自然科学基金资助项目 (3 0 3 70 73 8)
