Schmidt T, Karsunky H, Gau E, Zevnik B, Elsässer H P, Möröy T
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Germany.
Oncogene. 1998 Nov 19;17(20):2661-7. doi: 10.1038/sj.onc.1202191.
The gfi-1 gene encodes a zinc finger containing protein that is specifically expressed in T-lymphocytes and is a frequent target of proviral insertion in T-cell lymphoma provoked by infection with MoMuLV--a non acute transforming retrovirus. Expression of a gfi-1 transgene targeted to T-cells by the lck proximal promoter provokes a reduction of peripheral CD4 and CD8 positive T-cells but nevertheless weakly predisposes transgenic animals for the development of T-cell lymphoma. Forced coexpression of the serine/threonine kinase Pim-1 can partially restore normal T-cell numbers in double pim-1/gfi-1 transgenic mice. Moreover, the combinatorial expression of Pim-1 and Gfi-1 leads to accelerated development of T-cell lymphoma with a mean latency period of 114 days. A similar accelerated rate of lymphoma development was observed when lck-gfi-1 mice were crossed with mice that carry a L-myc gene targeted to be expressed at high levels in T-cells. The results show that gfi-1 can act with low activity as a dominant oncogene when overexpressed but also demonstrate that it is most efficient only in the presence of a cooperative partner protein as for example Pim-1 or L-Myc. In addition, the results suggest that Pim-1 and Gfi-1 are acting synergistically in both T-cell lymphomagenesis and T-cell development.
gfi-1基因编码一种含锌指结构的蛋白质，该蛋白质在T淋巴细胞中特异性表达，并且是莫洛尼鼠白血病病毒（MoMuLV，一种非急性转化逆转录病毒）感染引发的T细胞淋巴瘤中前病毒插入的常见靶点。由lck近端启动子靶向T细胞的gfi-1转基因的表达会导致外周CD4和CD8阳性T细胞减少，但仍使转基因动物轻度易患T细胞淋巴瘤。在双pim-1/gfi-1转基因小鼠中，丝氨酸/苏氨酸激酶Pim-1的强制共表达可部分恢复正常T细胞数量。此外，Pim-1和Gfi-1的组合表达会导致T细胞淋巴瘤加速发展，平均潜伏期为114天。当lck-gfi-1小鼠与携带在T细胞中高水平表达的L-myc基因的小鼠杂交时，观察到了类似的淋巴瘤加速发展速率。结果表明，gfi-1过度表达时可作为一种低活性的显性癌基因发挥作用，但也表明只有在存在协同伴侣蛋白（如Pim-1或L-Myc）时它才最有效。此外，结果表明Pim-1和Gfi-1在T细胞淋巴瘤发生和T细胞发育过程中均协同发挥作用。
