INTERFERON INDUCIBLE TRANSCRIPTION FACTORS: ROLES IN OCU

干扰素γ（IFNg）在全身免疫调节和肿瘤监视的宿主机制中起重要作用。它在治疗某些肿瘤性疾病中是有效的，并且其抗肿瘤作用被认为来自免疫效应细胞的活化。此外，被认为是肿瘤抑制因子的INFg诱导因子（IRF-1和ICSBP）在许多髓性白血病中缺失。在这项研究中，我们研究了IFNg是否可以直接作用于体内肿瘤细胞以抑制其生长。我们产生了在透镜中靶向表达IFNg和致癌性SV 40 T抗原（TAg）的双转基因（DT）小鼠。DT小鼠在子宫内发生透镜肿瘤。与TAg小鼠相反，肿瘤负荷随着年龄的增长而逐渐降低，导致成年DT小鼠的肿瘤完全消退。来自TAg或DT小鼠的脾和淋巴结T细胞不响应于TAg而增殖，表明两种品系都对转基因具有耐受性。我们还发现IRF-1、ICSBP和促凋亡蛋白caspase-1（ICE）的表达显著增加。 总之，我们的数据表明，这些眼睛中的肿瘤消退是由IFNg的直接抗肿瘤作用引起的，并且IFNg的主要影响是对肿瘤进展而不是对肿瘤起始的影响。 正在进行的研究试图描述潜在的机制。特别关注促凋亡途径在消除肿瘤性透镜细胞中的作用。

Interferon gamma (IFNg) plays important roles in the regulation of systemic immunity and host mechanisms of tumor surveillance. It is efficacious in treatment of certain neoplastic diseases and its anti-tumor effects is thought to derive from activation of immunological effector cells. Furthermore, INFg-inducible factors (IRF-1 and ICSBP) that are thought to be tumor suppressors are deleted in a number of myelogenic leukemias. In this study, we examined whether IFNg can act directly on tumor cells in vivo to suppress their growth. We generated double transgenic (DT) mice with targeted expression of IFNg and the oncogenic SV40 T-Antigen (TAg) in the lens. The DT mice developed lens tumors in utero. In contrast to the TAg mice, the tumor burden progressively decreased with age, resulting in complete regression of the tumor in adult DT mice. Splenic and lymph node T cells from TAg or DT mice did not proliferate in response to TAg, indicating that both strains are tolerant to the transgene. We also found significant increase in the expression of IRF-1, ICSBP and the pro-apoptotic protein, caspase-1 (ICE). Taken together, our data suggest that tumor regression in these eyes resulted from direct anti-tumor effects of IFNg and that the primary impact of IFNg is on tumor progression and not on tumor initiation. On going studies seek to characterize the underlying mechanism. Particular focus is on the role of pro-apoptotic pathways in elimination of neoplastic lens cells.