Wang J, Lu C, Min D, Wang Z, Ma X
Department of Genetics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Int Med Res. 2007 Jul-Aug;35(4):564-73. doi: 10.1177/147323000703500417.
We screened 117 breast tumour samples in Chinese females for mutations in the breast cancer 1 (BRCA1) gene and identified a novel mutation in the 5' untranslated region (5' UTR) in two patients with grade III infiltrating ductal breast carcinoma. We examined whether this 5' UTR mutation affected the translational efficiency of BRCA1 protein. A vector was constructed containing the mutated 5' UTR up-stream of luciferase and we compared its translational efficiency with a wild-type 5' UTR. The expression of BRCA1 protein in breast tumour samples was evaluated using immunohistochemistry. The mutated 5' UTR of BRCA1 resulted in less luciferase activity compared with the wild-type 5' UTR, while there were no significant differences in luciferase mRNA levels. BRCA1 protein was much less expressed in breast tumour tissue from patients with the 5' UTR mutation than in samples from patients without the mutation. Our results show that a mutation in the 5' UTR of the BRCA1 gene downregulates translational efficiency of the protein.
我们对117例中国女性乳腺癌样本进行筛查，以检测乳腺癌1（BRCA1）基因的突变情况，并在两名III级浸润性导管癌患者中，于5'非翻译区（5'UTR）发现了一种新的突变。我们研究了这种5'UTR突变是否会影响BRCA1蛋白的翻译效率。构建了一个载体，其中在荧光素酶上游含有突变的5'UTR，并将其翻译效率与野生型5'UTR进行比较。使用免疫组织化学评估乳腺癌样本中BRCA1蛋白的表达。与野生型5'UTR相比，BRCA1的突变5'UTR导致荧光素酶活性降低，而荧光素酶mRNA水平无显著差异。与无突变患者的样本相比，5'UTR突变患者的乳腺肿瘤组织中BRCA1蛋白表达明显减少。我们的结果表明，BRCA1基因5'UTR的突变会下调该蛋白的翻译效率。
