ポスターセッション

一覧　トップ

樹立ヒトpre-Bリンパ腫細胞(RC-K8)におけるアントラサイクリン系抗癌剤によるウロキナーゼタイププラスミノーゲンアクチベータ発現誘導： 新谷憲治、原田実根（岡山大・２内）

Induction of urokinase-type plasminogen activator by the anthracycline antibiotic in RC-K8 human pre-B lymphoma cells: Kenji NIIYA, Mine HARADA (2nd Dept. of Int. Med. Okayama University Medical School)

Urokinase-type plasminogen activator (uPA) catalyses the conversion of plasminogen to plasmin and plays a central role in many aspects of cellular regulation, such as fibrinolysis, cell migration and metastasis. uPA synthesis is regulated by infla-mmatory cytokines, IL-1 and TNF. Current evidence suggests that these inflammatory stimuli use reactive oxygen species (ROS) as signaling messengers to activate transcriptional factors. Anthracycline antibiotics are easily activated to semi-quinone radicals and generate ROS. We, therefore, examined effects of the anthracyclines such as doxorubicin (DOX), aclarubicin (ACL) and pirarubicin (PIR) on uPA expression in uPA-producing human pre-B lymphoma cell line RC-K8. uPA accumulation was remarkably increased after stimulation with subtoxic concentrations of DOX, ACL and PIR. Northern blot analysis revealed that both DOX and ACL increased uPA mRNA levels in a time-dependent manner. The transcriptional rate of uPA gene was increased after DOX stimulation, but the half-life of uPA mRNA was not changed. Antioxidants, N-acetylcysteine and pyrrolidine dithiocarbamate, inhibited DOX-induced uPA mRNA accumulation. These results suggest that the anthracycline induces uPA through activating uPA gene transcription in which ROS may be involved. Therefore, the anthracycline may influence many biological cell-functions mediated by the uPA/plasmin system by regulating uPA expression.