INTERFERON INDUCIBLE TRANSCRIPTION FACTORS: ROLES IN OCU

干扰素-γ(IFNG)在全身免疫调节和肿瘤监测的宿主机制中发挥重要作用。它对某些肿瘤疾病有效，其抗肿瘤作用被认为是通过激活免疫效应细胞而产生的。此外，被认为是肿瘤抑制因子的INFg诱导因子(IRF-1和ICSBP)在许多髓系白血病中被缺失。在这项研究中，我们研究了IFNG是否可以直接作用于体内的肿瘤细胞来抑制其生长。我们建立了双转基因(DT)小鼠，在晶状体中靶向表达IFNG和致癌的SV40T抗原(Tag)。DT小鼠在子宫内出现晶状体肿瘤。与TAG小鼠相比，肿瘤负担随着年龄的增长而逐渐减少，导致成年DT小鼠的肿瘤完全消退。TAG和DT小鼠的脾和淋巴结T细胞对TAG没有反应，表明两个品系对转基因都有耐受性。我们还发现IRF-1、ICSBP和促凋亡蛋白caspase-1(ICE)的表达显著增加。综上所述，我们的数据表明，这些眼睛的肿瘤消退是由于IFNG的直接抗肿瘤作用，并且IFNG的主要影响是肿瘤的进展，而不是肿瘤的起始。正在进行的研究试图刻画出潜在的机制。特别关注促凋亡通路在消除肿瘤晶状体细胞中的作用。

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.