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Enforced Expression of the M_r 33,000 Pim-1 Kinase Enhances Factor-independent Survival and Inhibits Apoptosis in Murine Myeloid Cells¹

Division of Medical Oncology, Department of Medicine, University of Washington and Veterans Affairs Medical Center, Seattle, Washington 98108 [M. L.], and the Division of Medical Oncology, University of Colorado Health Sciences, Denver, Colorado 80262 [A. K.]

Expression of the M_r 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 M_r 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.

¹ This work was supported in part by NIH Grants CA 45672 (to M. L.) and CA 42533 (to A. K.), by a grant from the Veterans Affairs Research Program (to M. L.), and by Grant DHP83 from the American Cancer Society (to A. K.).

² To whom requests for reprints should be addressed, at Medical Oncology (111ONC), Seattle VA Medical Center, 1660 Columbian Way South, Seattle, WA 98108. Fax: (206) 764-2851.

Received 3/20/97. Accepted 10/ 3/97.

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