The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters.
The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters.
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DOI：
10.1186/1471-2407-9-290
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发表时间：
2009-08-21
期刊：
影响因子：
3.8
通讯作者：
Mokbel K
中科院分区：
文献类型：
--
作者：
Al Sarakbi W;Sasi W;Jiang WG;Roberts T;Newbold RF;Mokbel K
SET结构域蛋白2（SET domain containing protein 2，SET D2）是一种参与转录延伸的组蛋白甲基转移酶。有证据表明，SETD2与p53相互作用，并选择性地调节其下游基因。因此，它可能与致癌过程有关。此外，该基因位于染色体3p的短臂上，并且我们先前证明了3号染色体的3p21.31区域与乳腺癌细胞的永久生长停滞相关。该区域包括密切相关的基因，即：MYL3、CCDC12、KIF9、KLHL18和SETD2。基于这些基因的生物学功能，SETD 2是最有可能发挥肿瘤抑制作用的基因，并解释了我们以前的发现。我们的目的是确定，使用定量PCR，是否SETD2的mRNA表达水平与乳腺癌中的肿瘤抑制功能一致。这是文献中第一个研究SETD 2与乳腺癌之间的直接关系的研究。共分析了153个样本。使用定量PCR测定SETD2的转录水平，并针对（CK19）进行标准化。将乳腺癌标本中的转录水平与正常背景组织进行比较，并在10年随访期内针对常规病理学参数和临床结果进行分析。SETD 2 mRNA的水平在恶性样本中显著较低（p = 0.0345），并且随着肿瘤分期的增加而降低。与无疾病> 10年的患者相比，来自发生转移、局部复发或死于乳腺癌的患者的样品中的SETD2表达水平显著较低（p = 0.041）。这项研究表明，在癌组织和发展为进行性疾病的患者中，SETD 2转录水平降低的趋势令人信服。这些发现与该基因在乳腺癌中可能的肿瘤抑制功能一致。
SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.
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DOI：
10.1073/pnas.0506350102
发表时间：
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影响因子：
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