Xu Qing, Liu Mei, Xu Ningzhi, Zhu Hongxia
Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
Mol Med Rep. 2014 Sep;10(3):1395-9. doi: 10.3892/mmr.2014.2371. Epub 2014 Jul 10.
Survivin is the smallest member of the inhibitor of apoptosis (IAP) family and is deregulated in breast cancer, where it is associated with a poor overall prognosis. It is well established that survivin overexpression predominately occurs at the transcriptional level. Numerous transcription factors bind to specific sequences in the promoter regions of genes and are involved in transcriptional regulation. Specificity protein (Sp) 1 binding sites have been found in the promoter region of the survivin gene. The present study aimed to investigate whether variations in Sp1 binding sites affect survivin expression. Nested polymerase chain reaction followed by DNA sequencing were performed to analyze the survivin gene promoter region in 42 breast cancer tissue samples. Furthermore, survivin expression was assessed using immunohistochemistry. High survivin protein expression was found in 66.7% (28/42) of breast cancer tissue samples. In addition, 15 variations in seven Sp1 binding sites were detected in 12 samples and Sp1 binding site variation was found to be associated with low survivin expression in the 42 samples. These findings suggested that variations in Sp1 binding sites may be associated with survivin expression.
生存素是凋亡抑制蛋白(IAP)家族中最小的成员,在乳腺癌中表达失调,与总体预后不良相关。众所周知,生存素的过表达主要发生在转录水平。许多转录因子与基因启动子区域的特定序列结合,并参与转录调控。在生存素基因的启动子区域发现了特异性蛋白(Sp)1结合位点。本研究旨在探讨Sp1结合位点的变异是否影响生存素的表达。采用巢式聚合酶链反应及DNA测序分析42例乳腺癌组织样本中生存素基因启动子区域。此外,采用免疫组织化学法评估生存素的表达。在66.7%(28/42)的乳腺癌组织样本中发现生存素蛋白高表达。另外,在12个样本中检测到7个Sp1结合位点的15个变异,且在42个样本中发现Sp1结合位点变异与生存素低表达相关。这些发现提示Sp1结合位点的变异可能与生存素表达有关。