Biological Effects of Retroviral Transfection of the Murine Interleukin-3 Gene into FDCP-Mix Cells

Spooncer, Elaine; Katsuno, Makoto; Hampson, Ian N.; Dexter, T. M.; Just, Ursula; Stocking, Carol; Kluge, N.; Ostertag, Wolfram

doi:10.1007/978-3-642-74623-9_10

Cited by 5 publications

(2 citation statements)

References 7 publications

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“…This experiment appeared to be of particular interest since we had previously learned that, although GM-CSF-, IL 2-or IL 3-dependent growing cells had become tumorigenic after transfer of the corresponding growth factor genes [9, [15][16][17][18][19][20][21][22], IL 4 autocrine growing cells did not grow in vivo [23]. Moreover, IL 4 has been shown to actively suppress tumor growth [24,2S] by a mechanism which possibly could involve eosinophils [24].…”

Section: Discussionmentioning

confidence: 99%

“…An alternate approach is the introduction and expression of growth factor genes in factor-dependent growing cell lines. The transfer of genes encoding GM-CSF, IL 2 or IL 3 into the respective factor-dependent cells led to autocrine growth and tumorigenicity [9,[15][16][17][18][19][20][21][22]. In contrast, the IL 4 gene transfer into an IL 4-dependent cell line resulted in autoc i n e growth but not in a leukemogenic phenotype [23], a phenomenon which has been attributed to the potent anti-tumor function of IL 4 [24, 251. I L 5 was originally described as a B cell growth factor (BCGF-11) or Tcell replacing factor (TRF; for review see [26,271.…”

Section: Introductionmentioning

confidence: 98%

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Retroviral interleukin 5 gene transfer into interleukin 5‐dependent growing cell lines results in autocrine growth and tumorigenicity

Blankenstein

Überla

et al. 1990

Eur J Immunol

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Two interleukin 5 (IL5)-specific retroviral expression vectors have been constructed containing the neomycin gene as selectable marker and either the mouse IL5 cDNA region or the rat genomic IL5 gene under the control of the thymidine kinase promoter. High viral titer supernatants derived from the transfected or infected packaging cell line psi 2 were used to infect the two cell lines B13 and T88M whose growth is dependent on exogenous IL 5. Infection resulted in G418 resistance and IL 5-independent growth with a high frequency. Clones were established which secrete between 2 and greater than 1000 U IL5. The proliferation of the IL5 autocrine growing cells could be inhibited by an antibody directed against the IL5 receptor indicating that they grow as a result of the endogenously produced IL5. Regardless of the amount of IL5 they produced, all of the clones were highly tumorigenic in nucle mice. The phenotype of the tumors was indistinguishable from that of the injected cells. T88M or B13 cells infected with a control virus neither produced IL5, nor became factor independent, nor produced tumors. Together, the IL5 gene transfer and expression into IL5-dependent growing cells are in accordance with the "autocrine growth" hypothesis and contrast analogous experiments with IL4.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Retroviral interleukin 5 gene transfer into interleukin 5‐dependent growing cell lines results in autocrine growth and tumorigenicity

Blankenstein

Überla

et al. 1990

Eur J Immunol

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Haemopoietic Cells as Targets for Gene Transfer

Daniel

Ponting

Hampson

et al. 1989

Vectors as Tools for the Study of Normal and Abnormal Growth and Differentiation

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Animal models for the biological effects of continuous high cytokine levels

Lübbert

Jonas

Herrmann

1990

Blut

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Transgenic animals or animals engrafted with retrovirus-derived expression vectors provide models for studying the in vivo effects of high and continuous serum levels of cytokines. Studies employing these models in order to analyze the biological effects for granulocytes-macrophages colony-stimulating factors (CSFs), granulocytes of interleukin (IL-)2, IL-3, IL-6 and erythropoietin are reviewed. In all of these models, overexpression of the different cytokines achieved by use of these approaches resulted in syndromes that were related to nonneoplastic hyperplasia of the respective target cell population. In some but not all models, these syndromes were lethal, mostly due to hypercellularity. These models allow conclusions about the biological effects of very high and continuous levels of these substances as well as about their regulation in different tissues.

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Biological Effects of Retroviral Transfection of the Murine Interleukin-3 Gene into FDCP-Mix Cells

Cited by 5 publications

References 7 publications

Retroviral interleukin 5 gene transfer into interleukin 5‐dependent growing cell lines results in autocrine growth and tumorigenicity

Retroviral interleukin 5 gene transfer into interleukin 5‐dependent growing cell lines results in autocrine growth and tumorigenicity

Haemopoietic Cells as Targets for Gene Transfer

Animal models for the biological effects of continuous high cytokine levels

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