Expression of TopBP1 in hereditary breast cancer.
Expression of TopBP1 in hereditary breast cancer.
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DOI：
10.1007/s11033-012-1622-z
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发表时间：
2012-07
影响因子：
2.8
通讯作者：
Brys M
中科院分区：
文献类型：
--
作者：
Forma E;Krzeslak A;Bernaciak M;Romanowicz-Makowska H;Brys M
TopBP1蛋白在结构和功能上与BRCA1相似，参与DNA复制、DNA损伤检查点反应和转录调控。TopBP1的异常表达可能导致基因组不稳定，并可能导致病理后果。本研究旨在探讨TopBP1基因在遗传性乳腺癌中mRNA和蛋白水平的表达。对127例乳腺癌标本进行实时定量PCR检测。TopBP1 mRNA在小叶癌中的表达明显低于导管癌（p < 0.05）。TopBP1 mRNA水平在低分化（III级）遗传性乳腺癌中明显低于中度（II级）和高分化（I级）遗传性乳腺癌（p < 0.05和p < 0.001）。我们使用免疫组织化学和Western blot技术分析TopBP1蛋白的表达。TopBP1蛋白在低分化乳腺癌（III级）中的表达显著升高（p < 0.05）。细胞质除核染色的样品百分比随着组织学分级的增加而增加。遗传性乳腺癌中TopBP1蛋白水平和细胞内定位与其他临床病理参数如雌激素和孕激素受体状态、腋窝淋巴结有无转移、肿瘤类型等无显著相关性。我们的数据表明，TopBP1 mRNA水平的降低和TopBP1蛋白水平的升高可能与遗传性乳腺癌的进展有关。
TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p < 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (p < 0.05 and p < 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (p < 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer.
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