scholarly journals Spi-1/PU.1 Is a Positive Regulator of the Fli-1 Gene Involved in Inhibition of Erythroid Differentiation in Friend Erythroleukemic Cell Lines

1999 ◽  
Vol 19 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Joëlle Starck ◽  
Alexandre Doubeikovski ◽  
Sandrine Sarrazin ◽  
Colette Gonnet ◽  
Govinda Rao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Virus ◽  
Erythroid Differentiation ◽  
Specific Pattern ◽  
Expression Vectors ◽  
Common Mechanism ◽  
Transformed Cell ◽  
Erythroleukemic Cell ◽  
Transformed Cell Lines

ABSTRACT Spi-1/PU.1 and Fli-1 are two members of the ETS family of transcription factors whose expression is deregulated by proviral insertion in most erythroleukemic cell lines induced by the spleen focus-forming virus (SFFV) and Friend murine leukemia virus (F-MuLV) components of the Friend viral complex, respectively. In this study, we present evidence that transcription of the Fli-1 gene is positively regulated by Spi-1/PU.1 in SFFV-transformed cell lines: (i) all SFFV-transformed cell lines expressing Spi-1/PU.1 are characterized by a specific pattern of Fli-1 gene transcripts initiated in the −200 region instead of position −400 as reported for F-MuLV-transformed cell lines; (ii) these Fli-1 transcripts initiated in the −200 region are downregulated in parallel with that of Spi-1/PU.1 during hexamethylenebisacetamide (HMBA) induced differentiation; and (iii) Fli-1 transcription is upregulated in SFFV cells lines following stable transfection of a Spi-1/PU.1 expression vector. Furthermore, we found by transient transfection assays that the −270/−41 region of the Fli-1 gene displays promoter activity which is transactivated by Spi-1/PU.1. This promoter is strictly dependent on the integrity of two highly conserved ETS DNA binding sites that bind the Spi-1/PU.1 protein in vitro. Finally, we show that transfection of constitutive or inducible Fli-1 expression vectors in SFFV-transformed cells inhibits their erythroid differentiation induced by HMBA. Overall, these data indicate that Fli-1 is a target gene of the Spi-1/PU.1 transcription factor in SFFV-transformed cell lines. We further suggest that deregulated synthesis of Fli-1 may trigger a common mechanism contributing to erythroleukemia induced by either SFFV or F-MuLV.

scholarly journals Murine Gammaherpesvirus (MHV-68) Transforms Cultured Cells in vitro

Intervirology ◽  
2015 ◽  
Vol 58 (2) ◽  
pp. 69-72 ◽  
Author(s):  
Veronika Mrázová ◽  
Tatiana Betáková ◽  
Marcela Kúdelová ◽  
Miroslava Šupolíková ◽  
Veronika Lachová ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cultured Cells ◽  
Virus Antigen ◽  
Immunofluorescence Assay ◽  
Dermal Fibroblasts ◽  
Murine Gammaherpesvirus ◽  
Transformed Cell ◽  
Transformed Cell Lines ◽  
Nih 3T3

Human dermal fibroblasts and mouse NIH/3T3 cells acquired the transformed phenotype (‘criss-cross' pattern of growth) after infection with ultraviolet-irradiated murine gammaherpesvirus (MuHV-4 strain 68; MHV-68). These cells with changed phenotype could be serially cultured for 5-6 passages (35-40 days), and then they entered into crisis and most of them died. In a small number of cultures, however, foci of newly transformed cells appeared from which two stable cell lines were derived. After 6-9 cell culture passages of the MHV-68 transformed cell lines, MHV-68 DNA and virus antigen could be detected by PCR and immunofluorescence assay along with the disappearance of actin bundles, indicating that both transformed cell lines might be oncogenic.

scholarly journals T cell growth factors from adult T cell leukemia virus-transformed cell lines

FEBS Letters ◽  
1984 ◽  
Vol 177 (2) ◽  
pp. 200-204 ◽  
Author(s):  
Yasuji Okai ◽  
Takashi Oka ◽  
Tadaatsu Akagi ◽  
Sayuri Kurata ◽  
Nobuo Fujiyoshi
Keyword(s):  
Growth Factors ◽  
T Cell ◽  
Cell Growth ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Transformed Cell ◽  
Adult T Cell Leukemia ◽  
T Cell Leukemia Virus ◽  
Transformed Cell Lines

scholarly journals Generation of tumorigenic porcine pancreatic ductal epithelial cells: toward a large animal model of pancreatic cancer

2018 ◽  
Author(s):  
Neeley Remmers ◽  
Jesse L. Cox ◽  
James A. Grunkemeyer ◽  
Shruthi Aravind ◽  
Christopher K. Arkfeld ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Animal Model ◽  
Cell Lines ◽  
Large Animal Model ◽  
Large Animal ◽  
Murine Models ◽  
Transformed Cell ◽  
Transformed Cell Lines

AbstractBackground. A large animal model of pancreatic cancer would permit development of diagnostic and interventional technologies not possible in murine models, and also would provide a more biologically-relevant platform for penultimate testing of novel therapies, prior to human testing. Here, we describe our initial studies in the development of an autochthonous, genetically-defined, large animal model of pancreatic cancer, using immunocompetent pigs.Methods. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs; epithelial origin was confirmed with immunohistochemistry. Three transformed cell lines subsequently were generated from these primary cells using expression of oncogenic KRAS and dominant negative p53, with/without knockdown of p16 and SMAD4. We tested these cell lines using in vitro and in vivo assays of transformation and tumorigenesis.Results. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion, with the greatest differences observed when all four genes (KRAS, p53, p16, and SMAD4) were targeted. All three transformed cell lines grew tumors when injected subcutaneously in nude mice, demonstrating undifferentiated morphology, mild desmoplasia, and staining for both epithelial and mesenchymal markers. Injection into the pancreas of nude mice resulted in distant metastases, particularly when all four genes were targeted.Conclusions. Tumorigenic porcine pancreatic cell lines were generated. Inclusion of four genetic “hits” (KRAS, p53, p16, and SMAD4) appeared to produce the best results in our in vitro and in vivo assays. The next step will be to perform autologous or syngeneic implantation of these cell lines into the pancreas of immunocompetent pigs. We believe that the resultant large animal model of pancreatic cancer could supplement existing murine models, thus improving preclinical research on diagnostic, interventional, and therapeutic technologies.

Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression

1988 ◽  
Vol 8 (5) ◽  
pp. 2261-2266
Author(s):  
M T Berlingieri ◽  
G Portella ◽  
M Grieco ◽  
M Santoro ◽  
A Fusco
Keyword(s):  
Cell Lines ◽  
Leukemia Virus ◽  
T Antigen ◽  
Myc Oncogene ◽  
Antigen Gene ◽  
Polyomavirus Middle T Antigen ◽  
Rat Thyroid ◽  
Transformed Cell Lines ◽  
Middle T Antigen

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

In vitro traits of adenovirus-transformed cell lines and their relevance to tumorigenicity in nude mice

Cell ◽  
1977 ◽  
Vol 10 (4) ◽  
pp. 669-678 ◽  
Author(s):  
Phillip H. Gallimore ◽  
James K. McDougall ◽  
Lan Bo Chen
Keyword(s):  
Cell Lines ◽  
Nude Mice ◽  
Transformed Cell ◽  
Transformed Cell Lines

scholarly journals Activation and association of Stat3 with Src in v-Src-transformed cell lines.

1996 ◽  
Vol 16 (4) ◽  
pp. 1595-1603 ◽  
Author(s):  
X Cao ◽  
A Tay ◽  
G R Guy ◽  
Y H Tan
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Tyrosine Kinases ◽  
New Members ◽  
Signal Transducers ◽  
Stat Proteins ◽  
Transformed Cell ◽  
Transformed Cell Lines

STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-transformed cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.

scholarly journals Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

1988 ◽  
Vol 8 (5) ◽  
pp. 2261-2266 ◽  
Author(s):  
M T Berlingieri ◽  
G Portella ◽  
M Grieco ◽  
M Santoro ◽  
A Fusco
Keyword(s):  
Cell Lines ◽  
Leukemia Virus ◽  
T Antigen ◽  
Myc Oncogene ◽  
Antigen Gene ◽  
Polyomavirus Middle T Antigen ◽  
Rat Thyroid ◽  
Transformed Cell Lines ◽  
Middle T Antigen

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

scholarly journals Novel B-cell precursors blocked at the stage of DJH recombination.

1988 ◽  
Vol 8 (12) ◽  
pp. 5216-5223 ◽  
Author(s):  
L Ramakrishnan ◽  
N Rosenberg
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Variable Region ◽  
Immunoglobulin Gene ◽  
Recombination System ◽  
Rearrangement Process ◽  
B Cell Precursors ◽  
Enzymatic Machinery

Abelson murine leukemia virus-transformed cells have provided the principal model for study of the early events in immunoglobulin gene rearrangements. In this communication, we describe a new type of Abelson virus-transformed pre-B-cell line that is arrested at the DJH stage of the recombination process. These cells differ from other pre-B transformants with respect to two properties associated with the immunoglobulin rearrangement process. First, in contrast to cell lines undergoing VH-to-DJH joining in vitro, none of these cell lines contained detectable levels of RNAs transcribed from their unrearranged VH genes. Second, only some of the cell lines recombined exogenous heptamer-nonamer sequences, indicating that many of them have lost at least a portion of the enzymatic machinery that mediates recombination. The correlation between the absence of unrearranged VH RNAs and the inability to rearrange endogenous immunoglobulin gene segments suggests that VH gene transcription is required both to maintain an active recombination system and for the final step in variable-region formation.

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