Bifunctional activity of transforming growth factor type ? on the growth of NRK-49F cells, normal and transformed by kirsten murine sarcoma virus

1988 ◽  
Vol 136 (1) ◽  
pp. 175-181 ◽  
Author(s):  
Pierre Jullien ◽  
Tone M. Berg ◽  
Colette de Lannoy ◽  
David A. Lawrence
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Factor Type ◽  
Murine Sarcoma

scholarly journals An agent or agents produced by virus-transformed cells cause unregulated ruffling in untransformed cells.

1986 ◽  
Vol 102 (4) ◽  
pp. 1224-1229 ◽  
Author(s):  
S E Myrdal ◽  
N Auersperg
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Rabbit Igg ◽  
Murine Sarcoma Virus ◽  
Normal Rat ◽  
Sarcoma Virus ◽  
Epidermal Growth ◽  
Factor Type ◽  
Kinetics Of

KNRK cells (a normal rat kidney [NRK] cell line transformed by Kirsten murine sarcoma virus) in sparse culture exhibit a highly ruffled morphology, but the cause of this ruffling is unknown. In this study, we have demonstrated that the continuous, excess ruffling on KNRK cells is caused by one or more soluble agents secreted by the KNRK cells themselves. To do this study, an assay for ruffling responses in live cell cultures was defined, and its reproducibility was demonstrated. This assay permitted observation of the kinetics of ruffling responses (percentage of cells ruffled as a function of time after stimulation). This method was used to compare the kinetics of ruffling induced by insulin, epidermal growth factor, fibroblast growth factor, glucose, and KNRK cell conditioned medium (CM). Ruffling was elicited on NRK cells by each of the polypeptide mitogens and nutrients, but, in each case, this ruffling subsided spontaneously within an hour. CM from KNRK cells also caused ruffling movements on untransformed NRK cells, but this ruffling continued for at least 20 h. This response was largely blocked by premixing the KNRK cell CM with rabbit IgG against rat transforming growth factor, type alpha, (TGF-alpha). KNRK cells made quiescent (ruffle free) by a pH shift (from 7.4 to 8.4) responded to insulin, glucose, and KNRK cell CM with kinetics similar to those observed for each of these factors in NRK cells. The unusual feature for the ruffle-inducing agent(s) produced by KNRK cells was that this activity was not subject, in either NRK or KNRK cells, to the cellular off-regulation that limits the responses to insulin or glucose. Thus, the continuous ruffling of KNRK cells is caused by their own unregulated ruffle-inducing agent or agents, which appear to include TGF-alpha. This work also demonstrates that kinetic analysis of cellular responses to exogenous factors can provide new insights into the regulatory mechanisms involved in the normal limitation of these responses.

scholarly journals Cell-mediated co-action of transforming growth factors: incubation of type beta with normal rat kidney cells produces a soluble activity that prolongs the ruffling response to type alpha.

1986 ◽  
Vol 102 (4) ◽  
pp. 1230-1234 ◽  
Author(s):  
S E Myrdal ◽  
D R Twardzik ◽  
N Auersperg
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Rat Kidney ◽  
Transforming Growth Factors ◽  
Tgf Beta ◽  
Murine Sarcoma Virus ◽  
Normal Rat ◽  
Sarcoma Virus ◽  
Epidermal Growth ◽  
Murine Sarcoma

Intense, continuous ruffling is a characteristic of many transformed cells, but untransformed cells ruffle intensely only briefly after exposure to growth factors. We reported previously that cells of a normal rat kidney (NRK) cell line transformed by Kirsten murine sarcoma virus secrete their own ruffle-inducing agent(s) that cause sustained ruffling in either themselves or untransformed NRK cells. In the present study, we examined the roles of the transforming growth factors TGF-alpha and TGF-beta in the induction and maintenance of ruffling in untransformed NRK cells and observed the following: TGF-alpha caused a transient epidermal growth factor (EGF)-like response, which could be blocked by prior exposure of cells to EGF or by antiserum directed against the COOH-terminus of TGF-alpha. TGF-beta caused no ruffling and did not itself prolong TGF-alpha ruffling. A new, buffer-soluble (transferable) mediator activity produced by incubation of TGF-beta with NRK cells for 6-h extended the duration of maximal TGF-alpha-induced ruffling by several-fold. This study demonstrates that TGF-alpha alone causes an EGF-like, transient ruffling response, but neither TGF-alpha or TGF-beta alone, nor the two together, cause transformation-associated sustained ruffling. Rather, TGF-alpha acts in concert with a new, TGF-beta-dependent activity. This new activity appears to inhibit normal cellular off-regulation of TGF-alpha-induced ruffling. Inhibition of the cellular off-regulation of a growth factor response could play a key role in the unregulated growth associated with malignancy.

Myeloproliferative virus, a cloned murine sarcoma virus with spleen focus-forming properties in adult mice.

1980 ◽  
Vol 33 (2) ◽  
pp. 573-582 ◽  
Author(s):  
W Ostertag ◽  
K Vehmeyer ◽  
B Fagg ◽  
I B Pragnell ◽  
W Paetz ◽  
...  
Keyword(s):  
Adult Mice ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Murine Sarcoma

Functional organization of the Harvey murine sarcoma virus genome.

1980 ◽  
Vol 35 (1) ◽  
pp. 76-92 ◽  
Author(s):  
E H Chang ◽  
J M Maryak ◽  
C M Wei ◽  
T Y Shih ◽  
R Shober ◽  
...  
Keyword(s):  
Functional Organization ◽  
Virus Genome ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Murine Sarcoma
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