Lilly M, Kraft A
Department of Medicine, University of Washington and Veterans Affairs Medical Center, Seattle 98108, USA.
Cancer Res. 1997 Dec 1;57(23):5348-55.
Expression of the Mr 33,000 human Pim-1 protein is induced in hematopoietic cells by a variety of growth factors and cytokines. We have introduced the human pim-1 cDNA via retroviral transduction into interleukin (IL)-3-dependent FDC-P1 cells and examined the resulting phenotype. Compared with cells infected with a neo-encoding retrovirus (FD/neo), cells infected with a pim-1-transducing virus (FD/hpim) showed longer survival or autonomous growth in suspension culture in the absence of IL-3, as well as IL-3-independent clonogenic growth in semisolid medium. The unique murine Mr 44,000 Pim-1 protein, as well as human proteins with short C- or N-terminal truncations, also was biologically active. This effect of Pim-1 expression was associated with a decrease in apoptotic cells and an increase in G0/G1-phase cells, and the increase in G0/G1-phase cells caused by enforced expression of Pim-1 was due to a decrease in apoptosis rather than to a decrease in transit of the G1-S-phase checkpoint. The Pim-1 kinase appears to function primarily as a survival factor in factor-dependent FDCP-1 cells subjected to either cytokine withdrawal or exposure to cytotoxic agents.
多种生长因子和细胞因子可诱导造血细胞中33000 Mr的人Pim-1蛋白表达。我们通过逆转录病毒转导将人pim-1 cDNA导入白细胞介素（IL）-3依赖的FDC-P1细胞，并检测其产生的表型。与感染编码新霉素的逆转录病毒（FD/neo）的细胞相比，感染pim-1转导病毒（FD/hpim）的细胞在无IL-3的悬浮培养中存活时间更长或能自主生长，并且在半固体培养基中能进行不依赖IL-3的集落形成生长。独特的44000 Mr鼠源Pim-1蛋白以及C末端或N末端截短的人蛋白也具有生物活性。Pim-1表达的这种效应与凋亡细胞减少和G0/G1期细胞增加有关，并且Pim-1的强制表达导致的G0/G1期细胞增加是由于凋亡减少而非G1-S期检查点过渡减少。Pim-1激酶在依赖因子的FDCP-1细胞中，无论是在细胞因子撤除还是暴露于细胞毒性剂的情况下，似乎主要作为一种存活因子发挥作用。
