講演情報
[O5-1]肺がんの新規予後マーカー、治療標的分子URST1の同定
○高野 淳1,2,3, 宮城 洋平4, 醍醐 弥太郎1,2,3 (1.東京大学 医科学研究所 抗体ワクチンセンター, 2.滋賀医科大学・臨床腫瘍学講座・腫瘍内科, 3.滋賀医科大学・先端がん研究センター, 4.神奈川がんセンター・がん分子病態部)
To identify new cancer biomarkers and therapeutic targets for lung cancer, we screened up-regulated molecules in lung cancers by gene expression microarray and selected up-regulated in solid tumor 1 (URST1) as a candidate. Immunohistochemical staining of URST1 showed that URST1 expression was observed in 231 (64.5%) of 358 non-small cell lung cancers (NSCLC) and 11 (84.6%) of 13 small cell lung cancers. High level of URST1 expression was associated with poor prognosis for NSCLC patients (P = 0.0003). Multivariate analysis confirmed that strong URST1 expression was an independent prognostic factor for NSCLC patients that had undergone radical surgery. Knockdown of URST1 expression by siRNAs against URST1 significantly suppressed the growth of lung cancer cells. Inhibition of URST1 expression also suppressed the invasive ability of lung cancer cells. Treatment of lung cancer cells with small molecule inhibitor against URST1 suppressed the cell growth partly through G2/M arrest and cell death. In contrast, enforced expression of URST1 significantly promoted lung cancer cell growth. URST1 level was increased at mitotic phase, suggesting its involvement in the mitosis of cancer cells. URST1 could play an essential role in malignant potential of lung cancer and it might be useful as a prognostic biomarker and therapeutic target.