Laboratory of Molecular Medicine, Human Genome Center, University of Tokyo, Tokyo, Japan.
Cancer Sci. 2012 Mar;103(3):577-86. doi: 10.1111/j.1349-7006.2011.02167.x. Epub 2012 Jan 9.
To identify potential molecular targets for diagnosis, treatment and/or prevention of lung and esophageal carcinomas, we screened for genes that were overexpressed in tumors through gene expression analyses of 120 lung cancers and 19 esophageal squamous-cell carcinomas using a cDNA microarray consisting of 27,648 cDNA or expressed sequence tags. In this process, we identified a gene, Opa interacting protein 5 (OIP5), to be highly transactivated in the majority of lung and esophageal cancers. Immunohistochemical staining using 336 archived non-small cell lung cancers and 305 esophageal squamous-cell carcinomas specimens demonstrated that OIP5 expression was significantly associated with poor prognosis of lung and esophageal cancer patients (P = 0.0053 and 0.0168, respectively), and multivariate analysis confirmed its independent prognostic value for non-small cell lung cancers (P = 0.0112). Suppression of OIP5 expression with siRNA effectively suppressed the growth of cancer cells, whereas the exogenous expression of OIP5 enhanced the growth of cancer cells. In addition, OIP5 protein is likely to be stabilized through its interaction with Raf1. OIP5 is a promising target for developing new prognostic biomarkers and anti-cancer drugs.
为了鉴定肺癌和食管癌诊断、治疗和/或预防的潜在分子靶标，我们利用包含 27648 个 cDNA 或表达序列标签的 cDNA 微阵列，对 120 例肺癌和 19 例食管鳞癌进行基因表达分析，以筛选出在肿瘤中过表达的基因。在这个过程中，我们鉴定了一个基因，Opa 相互作用蛋白 5（OIP5），它在大多数肺癌和食管癌中高度转录激活。利用 336 例存档的非小细胞肺癌和 305 例食管鳞癌标本进行的免疫组织化学染色表明，OIP5 的表达与肺癌和食管癌患者的不良预后显著相关（P = 0.0053 和 0.0168，分别），多变量分析证实其对非小细胞肺癌具有独立的预后价值（P = 0.0112）。用 siRNA 抑制 OIP5 的表达可有效抑制癌细胞的生长，而外源性表达 OIP5 则增强了癌细胞的生长。此外，OIP5 蛋白可能通过与 Raf1 的相互作用而稳定。OIP5 是开发新的预后生物标志物和抗癌药物的有前途的靶标。
