Enforced expression of the Mr 33,000 Pim-1 kinase enhances factor-independent survival and inhibits apoptosis in murine myeloid cells.

Abstract

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.