School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
Cancer Sci. 2012 Aug;103(8):1574-9. doi: 10.1111/j.1349-7006.2012.02309.x. Epub 2012 May 30.
The present study investigated the transcriptional regulation of low-fidelity translesion DNA synthesis (TLS) polymerases in human esophageal carcinoma. Significantly higher mRNA expression of polymerase zeta (Polξ), RAD18, polymerase iota (Polι), and polymerase kappa (Polκ) was found in esophageal carcinomas. The increased expression of Polι in tumor samples was further confirmed by immunohistochemistry. The promoter of POLI that encodes Polι was found to be hypomethylated, although the overexpression of this gene was unlikely to be associated with methylation in tumors. We further identified Sp1 and Oct-1 binding sites present in the POLI promoter. We observed that the binding affinity of Sp1 to the POLI promoter was significantly increased in cancerous tissues and that Sp1 activated POLI gene transcription in cultured cell lines. The present study demonstrates overexpression of the TLS genes in esophageal carcinoma and identifies a key role for Sp1 in upregulating POLI gene expression.
本研究调查了低保真跨损伤 DNA 合成（TLS）聚合酶在人食管鳞癌中的转录调控。在食管癌中发现聚合酶 ζ（Polξ）、RAD18、聚合酶 ι（Polι）和聚合酶 κ（Polκ）的 mRNA 表达显著升高。免疫组织化学进一步证实了肿瘤样本中 Polι 的表达增加。POLI 编码 Polι 的启动子被发现低甲基化，尽管该基因的过表达不太可能与肿瘤中的甲基化有关。我们进一步鉴定了 POLI 启动子中存在的 Sp1 和 Oct-1 结合位点。我们观察到 Sp1 与 POLI 启动子的结合亲和力在癌组织中显著增加，并且 Sp1 激活了培养细胞系中 POLI 基因的转录。本研究表明 TLS 基因在食管鳞癌中过度表达，并确定了 Sp1 在上调 POLI 基因表达中的关键作用。
