Autocrine Growth-Factor Secretion After Transformation of Human Cytokine-Dependent Cells by Viral and Cellular Oncogenes

McCubrey, JA; Steelman, LS; Xy, Wang; Davidian, Ew; Hoyle, Paul; Cr, White; Prevost, Kd; Algate, Paul A.; Robbins, P; Mylott, D; Mk, White

doi:10.3892/ijo.7.3.573

Cited by 8 publications

(11 citation statements)

References 43 publications

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“…Retroviruses were passed sequentially from one cell line to the other to amplify their titers as described. 9,10,12 FDC-P1 cells were infected with viral stocks as described. 9,10,12 TF-1 cells were infected with amphitropic stocks prepared from the PA317 cell line.…”

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

“…9,10,12 FDC-P1 cells were infected with viral stocks as described. 9,10,12 TF-1 cells were infected with amphitropic stocks prepared from the PA317 cell line. 12 The nomenclature of the FDC-P1 cells is FD/⌬Raf-1:ER for cells infected with the ⌬Raf-1:ER virus.…”

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

“…9,10,12 TF-1 cells were infected with amphitropic stocks prepared from the PA317 cell line. 12 The nomenclature of the FDC-P1 cells is FD/⌬Raf-1:ER for cells infected with the ⌬Raf-1:ER virus. The nomenclature of the TF-1 cells is TF/⌬Raf-1:ER or TF/⌬A-Raf:ER for cells infected with the ⌬Raf-1:ER or ⌬A-Raf:ER viruses, respectively.…”

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

“…Thirty-five cycles of PCR were performed to detect the cDNAs as described. 12,[14][15][16] The PCR products were electrophoresed on 1% agarose gels and visualized after ethidium bromide staining of the gel.…”

Section: Polymerase Chain Reaction Amplification Of Cytokine Mrna Tramentioning

confidence: 99%

“…11 This cell line has a low spontaneous frequency of conversion to factor independence and TF-1 cells do not normally form tumors after injection in immunocompromised mice. [11][12][13][14][15][16][17] Thus, these cell lines represent models for analysis of the effects of aberrant oncogene expression on human hematopoietic cell growth, differentiation and malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

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Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Weinstein‐Oppenheimer

Steelman

Algate

et al. 2000

Leukemia

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The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated. The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines. The conditionally active Raf proteins were regulated by ␤-estradiol as cDNAs containing the Raf catalytic, but lacking negative-regulatory domains, were ligated to the hormone binding domain of the estrogen receptor (⌬Raf:ER). Continuous ⌬Raf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/⌬Raf:ER cells as they grew in large aggregated masses (Ͼ100 cells) whereas the parental cytokinedependent FDC-P1 cells grew in smaller grape-like clusters (Ͻ10 cells). FD/⌬Raf-1:ER cells growing in response to Raf activation displayed decreased levels of the Mac-2 and Mac-3 molecules on their cell surface. In contrast, when these cells were cultured in IL-3, higher levels of these adhesion molecules were detected. Expression of activated Raf oncoproteins also abrogated cytokine dependency and prevented apoptosis of TF-1 cells. Moreover, the differentiation status of these Raf-responsive cells was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate (PMA) and ␤-estradiol resulted in decreased levels of the CD11b and CD18 integrin molecules on the cell surface. In contrast when the Raf-responsive cells were induced to differentiate with PMA and GM-CSF, in the absence of ⌬Raf:ER activation, increased levels of the CD11b and CD18 molecules were detected. Retinoic acid (RA) inhibited 3 H-thymidine incorporation in response to GM-CSF. Interestingly, Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA. Thus deregulated Raf expression can alter cytokine dependency, integrin expression and the stage of differentiation. These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation. Leukemia

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Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

Section: Polymerase Chain Reaction Amplification Of Cytokine Mrna Tramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Weinstein‐Oppenheimer

Steelman

Algate

et al. 2000

Leukemia

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Differential abilities of activated Raf oncoproteins to abrogate cytokine dependency, prevent apoptosis and induce autocrine growth factor synthesis in human hematopoietic cells

et al. 1998

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Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs

Blalock

Weinstein‐Oppenheimer

et al. 1999

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Over the past decade, there has been an exponential increase in our knowledge of how cytokines regulate signal transduction, cell cycle progression, differentiation and apoptosis. Research has focused on different biochemical and genetic aspects of these processes. Initially, cytokines were identified by clonogenic assays and purified by biochemical techniques. This soon led to the molecular cloning of the genes encoding the cytokines and their cognate receptors. Determining the structure and regulation of these genes in normal and malignant hematopoietic cells has furthered our understanding of neoplastic transformation. Furthermore, this has allowed the design of modified cytokines which are able to stimulate multiple receptors and be more effective in stimulating the repopulation of hematopoietic cells after myelosuppressive chemotherapy. The mechanisms by which cytokines transduce their regulatory signals have been evaluated by identifying the involvement of specific protein kinase cascades and their downstream transcription factor targets. The effects of cytokines on cell cycle regulatory molecules, which either promote or arrest cell cycle progression, have been more recently examined. In addition, the mechanisms by which cytokines regulate apoptotic proteins, which mediate survival vs death, are being elucidated. Identification and characterization of these complex, interconnected pathways has expanded our knowledge of leukemogenesis substantially. This information has the potential to guide the development of therapeutic drugs designed to target key intermediates in these pathways and effectively treat patients with leukemias and lymphomas. This review focuses on the current understanding of how hematopoietic cytokines such as IL-3, as well as its cognate receptor, are expressed and the mechanisms by which they transmit their growth regulatory signals. The effects of aberrant regulation of these molecules on signal transduction, cell cycle regulatory and apoptotic pathways in transformed hematopoietic cells are discussed. Finally, anti-neoplastic drugs that target crucial constituents in these pathways are evaluated.

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Autocrine Growth-Factor Secretion After Transformation of Human Cytokine-Dependent Cells by Viral and Cellular Oncogenes

Cited by 8 publications

References 43 publications

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Differential abilities of activated Raf oncoproteins to abrogate cytokine dependency, prevent apoptosis and induce autocrine growth factor synthesis in human hematopoietic cells

Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs

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