Nussbaum T, Vreden S, Farsad M, Schirmacher P, Breuhahn K
Mitglied des Zentrums für Molekulare Medizin der Universität zu Köln (ZMMK).
Verh Dtsch Ges Pathol. 2005;89:254-60.
Several studies have examined the expression profiles of human hepatocellular carcinomas (HCCs) using high density microarray technology, but subtyping with potential mechanistic and therapeutic impact has not been achieved so far. Here we have analysed the expression pattern of human HCCs and HCC cell lines in comparison to normal liver. A characteristic of one group of HCCs and all HCC cell lines was overexpression of insulin-like growth factor (IGF)-II. Moreover, IGF-II expression was mutually exclusive to induction of several IFN-related genes. In vitro, treatment of HCC cells with IFNgamma leads to a strong reduction of IGF-II expression. Equally, specific reduction of IGF-II was achieved using RNAinterference in HCC cells. Therefore, IGF-II may represent an excellent target for IFNgamma-treatment and specific siRNA-mediated therapeutic intervention.
多项研究已使用高密度微阵列技术检测了人类肝细胞癌(HCC)的表达谱,但迄今为止尚未实现具有潜在机制和治疗意义的亚型分类。在此,我们分析了人类HCC和HCC细胞系相对于正常肝脏的表达模式。一组HCC和所有HCC细胞系的一个特征是胰岛素样生长因子(IGF)-II的过表达。此外,IGF-II的表达与几种干扰素相关基因的诱导相互排斥。在体外,用干扰素γ处理HCC细胞会导致IGF-II表达大幅降低。同样,在HCC细胞中使用RNA干扰也实现了IGF-II的特异性降低。因此,IGF-II可能是干扰素γ治疗和特异性siRNA介导的治疗干预的理想靶点。