Showing papers on "Friend leukemia published in 1995"

Phosphoinositide Signaling in Nuclei of Friend Cells: Tiazofurin Down-Regulates Phospholipase C β1

Abstract: Previous investigations have demonstrated the presence of conventional lipid kinases and phospholipase C (PLC) activities in nuclei of Friend erythroleukemia cells. Moreover, when Friend erythroleukemia cells are treated for 96 h with the antitumor drug tiazofurin, the induction of erythroid differentiation is accompanied by changes in amounts of both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate due to the inhibition of an uncharacterized nuclear PLC activity. Here, we show that the nuclear PLC beta 1 isoform is down-regulated by tiazofurin (5 microM) treatment of Friend erythroleukemia cells as shown by both Western blot and Northern blot analyses for PLC beta 1 message. This indicates that PLC beta 1 down-regulation is tightly linked with erythroid differentiation of Friend erythroleukemia cells and that the autonomous nuclear signaling via inositol lipid cycle can be controlled by the antitumor drug tiazofurin.

Local and systemic response of mice to interferon-alpha 1-transfected Friend leukemia cells.

Abstract: DBA/2 mice were injected subcutaneously with an interferon (IFN)-alpha/beta-resistant line of Friend erythroleukemia cells (FLC) transfected with the mouse IFN-alpha 1 gene. These tumor cells produced IFN constitutively, and mice had persistently high levels of IFN in the circulation. We examined the IFN-induced host mechanisms responsible for the local inhibition of growth of these IFN-alpha-transfected FLC and some of the unusual systemic effects of constant interferonemia such as extramedullary hematopoiesis in the liver, an increase in myeloid cells in the spleen, and persistently elevated splenic natural killer (NK) cell activity. In addition, both DBA/2 +/bg and beige mice developed a rapid and specific resistance to intravenous challenge with parental FLC. In previous experiments DBA/2 beige mice could not be protected by exogenous IFN-alpha/beta. The differences in the response of mice to the constitutive production of IFN-alpha by IFN-alpha-transfected tumor cells and their response to exogenous IFN is discussed in terms of the effects of IFN on the host and of antitumor therapy.

A Mouse Erythroleukemia Cell Line Possessing Friend Spleen Focus‐forming Virus gp55 Transgene and Temperature‐sensitive Mutant p53 Gene

Abstract: Two different erythroleukemia cell lines have been established from the splenic lesions of transgenic mice possessing the Friend spleen focus-forming virus (F-SFFV) gp55 gene. One showed a neardiploid karyotype and a temperature-sensitive (ts) p53 mutation, and the other, a hyper-triploid karyotype with double p53 mutations found by single-strand conformation polymorphism (SSCP) analysis. The cell lines both retained No.11 chromosomes on which p53 genes are localized. Another p53 allele in the cell line with the ts-p53 mutation appeared intact in the SSCP analysis of the genomic exon 5. The cells with the ts-mutant p53 gene showed no apparent change with temperature shift in their growth or dimethylsulfoxide-induced differentiation, although the wild-type p53 gene on the other allele was not expressing. This ts-p53val-135 gene made p53-deficient fibroblasts anchorageindependent at 37°C but not at 32°C. This non-virus-producing, mouse erythroleukemia cell line will be useful for the study of mutated p53 function during the induction of erythrodifferentiation or apoptotic change.

Correlation between the sensitivity or resistance to IL‐2 and the response to cyclophosphamide of 4 tumors transplantable in the same murine host

Abstract: We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb lymphoma and Friend leukemia cells (non-responsive or poorly responsive, respectively), pI I-R-Eb and Eb lymphoma cells (both highly responsive to IL-2). CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti-tumor effect was observed in mice injected with Eb or pI I-R-Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor response in mice transplanted with pI I-R-Eb cells. Injection of monoclonal antibodies (MAbs) to IFN-γ completely abolished the anti-tumor effects of IL-2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells from mice transplanted with the IL-2-responsive tumors. This activity was abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice injected with pI I-R-Eb cells. Our results indicate an inverse correlation between sensitivity to IL-2 and response to CTX and emphasize the importance of initial host-tumor interaction in determining the type of response to IL-2 or CTX. © 1995 Wiley-Liss, Inc.