Biomedical subjects

F Dautry

Publications and source records attributed to F Dautry.

43 records · Page 3Linked to original sources

PubMed1988

Induction of tumor necrosis factor-alpha and -beta and interferon-gamma mRNA by interleukin 2 in murine lymphocytic cell lines.

We have investigated genes regulated by interleukin-2 (IL2) in the murine lymphocytic cell line CTLL-2 by differential screening of a cDNA library. One of the clones we have identified is a partial cDNA of tumor necrosis factor-beta, (TNF-beta), a gene previously shown to be expressed in response to lymphocyte activation. This led us to investigate the regulation by IL2 of TNF-alpha, TNF-beta, and interferon-gamma (IFN-gamma) mRNA. In two murine lymphocytic cell lines all three genes are induced during the primary response to IL2. This regulation of lymphokine expression by IL2 is correlated with cell proliferation and not with the cytotoxic activity. As activated T lymphocytes express receptors to both TNF and IFN-gamma, our observation raises the possibility that these lymphokines are involved in an autocrine regulation of cytotoxic lymphocytes proliferation.

Amino Acid Sequence↗

PubMed1987

c-myc oncogene expression inhibits the initiation of myogenic differentiation.

The role of c-myc oncogene expression in myogenic differentiation has been established by transfecting rat myoblasts of the L6 cell line with plasmid pMT-myc, in which the c-myc coding sequences were under the control of the metallothionein I promoter. We observed that the constitutive expression of the exogenous c-myc gene inhibits muscular differentiation. A diminution of the endogenous c-myc gene expression occurs within the first 24 h after the transfer of the cells to a differentiating medium. This early decrease of c-myc expression is required for cell differentiation to occur. We have also observed that exogenous myc gene expression has no effect on endogenous myc expression.

Animals↗

PubMed1986

Modulation of c-fos and c-myc mRNA levels in normal human lymphocytes by calcium ionophore A23187 and phorbol ester.

A transient expression of the proto-oncogenes c-fos and c-myc is rapidly induced by growth factors or mitogens in different cell types including lectin-stimulated lymphocytes. To elucidate the early events of lymphocyte activation, we determined (by Northern blot analysis) the steady-state levels of c-fos and c-myc mRNA in normal human peripheral blood lymphocytes (PBL) stimulated with the Ca2+ ionophore A23187 and/or 12-O-tetradecanoylphorbol-13-acetate (TPA), whose biological activities are well defined. We report that ionophore A23187 (0.5 microM) or, to a significantly lesser extent, TPA (0.5 ng/ml), neither of which is mitogenic alone at these concentrations, nevertheless can induce a transient accumulation of the proto-oncogene transcripts. These results indicate that a significant accumulation of c-fos and c-myc mRNA can occur without subsequent lymphocyte proliferation. The combination of these two mitogens increases the induced levels of both types of c-onc mRNAs. The level of mRNA accumulation correlates with the degree of proliferation induced by mitogenic combinations of ionophore A23187 and TPA, as measured by [3H]thymidine incorporation. Thus, these compounds act synergistically both with respect to c-fos and c-myc mRNA accumulation and to mitogenicity in human PBL. We also studied the level of c-fos transcripts following stimulation of the T lymphocyte T3/Ti receptor complex, using monoclonal anti-T3 antibodies. We observed that mitogenic doses of anti-T3 also induce an accumulation of c-fos mRNA, whose induction also is synergized by TPA. These results suggest that transient accumulation of c-fos; as well as c-myc, mRNA is a normal event of the immune response. They confirm that Ca2+ ionophore combined with TPA can mimic some molecular features of the early steps of normal human PBL activation.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1986

Correlation between an HLA-DQ alpha length polymorphism of messenger RNA and serologically defined specificities (DQw1, DRw53, DR3+5).

mRNAs for the two chains of the HLA-DQ molecule were analyzed, in particular the DQ alpha mRNA whose polymorphism had previously been suggested (Schenning et al. 1984). Northern blot transfers of the mRNA of 12 LCLs and of B lymphocytes from a healthy donor were carried out. We report that a length polymorphism of DQ alpha mRNA exists, and we show that it can be correlated with serologically defined specificities (DQw1, DRw53, DR3+5). This correlation could be explained by a linkage disequilibrium, as these specificities are considered to be different from those carried by the DQ molecule (except for the DQw1 specificity).

DNA Restriction Enzymes↗

PubMed1986

Growth stimulation of rat primary embryo fibroblasts by the human myc gene.

We have studied the ability of plasmids encoding a normal human myc protein to stimulate growth of primary rat embryo fibroblasts. We measured growth stimulation by the number of G418-resistant colonies obtained after co-transfection with plasmid pSV2neo and by the percentage of these colonies that grew in long-term culture (immortalization). Using a normal human myc gene, we detected a weak growth stimulation at the colony formation stage and a low frequency of immortalization. Replacement of the myc promoter by a heterologous promoter (mouse metallothionein I promoter) and deletion of the first non-coding exon led to a more efficient growth stimulation by both criteria. Thus, disregulation of c-myc is essential for an altered pattern of growth. Using zinc, a metallothionein inducer, we observed a slight increase in the growth rate of some transfectants, which can be measured by thymidine incorporation. However, the relative inefficiency of immortalization we observed suggests that either a high level of myc expression or participation of other genes is required for establishment in culture. Under our experimental conditions, we could not detect a transforming activity for the human myc gene and none of our myc-containing cell lines was tumorigenic in nude mice.

Animals↗

PubMed1986

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗

PubMed1983

The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors.

The oncogene of the HL-60 human promyelocytic leukemia cell line has been passed serially through NIH/3T3 mouse fibroblasts. Oncogene-specific probes prepared from the resulting tertiary transfectants by molecular cloning have been used to show that loss of the transfected oncogene from NIH/3T3 cells correlates with reversion to nontransformed morphology. Analysis of cells transfected by the oncogenes of other tumors and tumor cell lines indicates that the transforming gene of the HL-60 leukemia cell line is closely related to oncogenes of a Burkitt's lymphoma, an acute myelogenous leukemia, an adenocarcinoma of the colon, a neuroblastoma, and two sarcomas. This oncogene is distantly related to the viral oncogenes of Kirsten and Harvey sarcoma viruses. It has been termed N-ras. The active N-ras oncogene coexists with altered versions of the myc oncogene in the HL-60 and AW Ramos human tumors. This suggests a multistep mechanism involving both ras and myc genes in the creation of these tumors.

Animals↗