Expression of HDAC1 and CBP/p300 in human colorectal carcinomas
Expression of HDAC1 and CBP/p300 in human colorectal carcinomas
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DOI：
10.1136/jcp.2005.029165
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Kimura, Wataru
中科院分区：
文献类型：
--
作者：
Ishihama, Katsuyoshi;Yamakawa, Mitsunori;Kimura, Wataru
背景：组蛋白修饰酶组蛋白去乙酰酶(HDAC)和组蛋白乙酰转移酶(HAT)控制着人类恶性肿瘤基因转录的激活和抑制。目的：分析HDAC/HAT相关分子HDAC1、CREB结合蛋白(CBP)和p300在结直肠癌中的表达，并探讨其表达水平与临床病理参数的关系。采用原位杂交(ISH)和逆转录-聚合酶链式反应(RT-PCR)检测这些基因的表达水平。免疫反应性用染色指数(SI)进行半定量评价。结果：本组肿瘤中HDAC1、CBP和p300的平均SIS均明显高于正常大肠黏膜组织。ISH分析证实HDAC1和CBP mRNAs存在于结直肠癌细胞和正常上皮细胞中。逆转录聚合酶链式反应(RT-PCR)检测到大部分病例中p300基因表达水平显著升高。在结直肠癌患者中，p300(SI>；11.9)的过度表达与预后不良有关，而CBP的高表达(SI>；16.6)则预示着患者的长期生存。结论：这三种组蛋白修饰分子在结直肠癌中表达上调，提示监测CBP和p300有助于预测结直肠癌患者的预后。
Background: The histone- modifying enzymes histone deacetylase ( HDAC) and histone acetyltransferase ( HAT) control gene transcriptional activation and repression in human malignancies.Aims: To analyse the expression of HDAC/ HAT- associated molecules such as HDAC1, CREB- binding protein ( CBP) and p300 in human colorectal carcinomas, and investigate the relationship between their expression levels and clinicopathological parameters.Methods: Expression levels of HDAC1, CBP, and p300 in human colorectal cancer were investigated by immunohistochemistry. In situ hybridisation ( ISH) and reverse transcription ( RT)- PCR analyses were also carried out to confirm mRNA expression levels of these genes. Immunoreactivity was evaluated semiquantitatively using a staining index ( SI). The relationships between the SIs and clinicopathological findings were analysed and survival curves were calculated using the Kaplan - Meier method and log- rank tests.Results: The mean SIs for HDAC1, CBP, and p300 in this series of tumours were much higher than those in normal colonic mucosa. The presence of HDAC1 and CBP mRNAs on colorectal carcinoma cells as well as normal epithelial cells was confirmed by ISH analysis. A marked increase in p300 mRNA levels was detected in a majority of cases by RT- PCR. Among the patients with colorectal cancer, overexpression of p300 ( SI>11.9) correlated with a poor prognosis, whereas high CBP expression levels ( SI>16.6) indicated longterm survival.Conclusion: Results showed the up- regulation of these three histone- modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.