The cellular response to induction of the p21 c-Ha-ras oncoprotein includes stimulation of jun gene expression.

Sistonen, Lea; Hölttä, Erkki; Tp, Mäkelä; Keski‐Oja, Jorma; Alitalo, Kari

doi:10.1002/j.1460-2075.1989.tb03442.x

Cited by 107 publications

(62 citation statements)

References 76 publications

(37 reference statements)

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“…Both c-jun and junB mRNA levels were shown previously to be induced by transient expression of Ras (Sistonen et al, 1989). We con®rm that the accumulation of cJun in stable Ras-transformed ®broblasts results from an increase in c-jun mRNA level as well as from the stabilization of its translation product.…”

Section: Discussionsupporting

confidence: 73%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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Section: Discussionsupporting

confidence: 73%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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“…There are contradictory data on the location of the di erent response elements that need to be clari®ed (Herber et al, 1994;Albanese et al, 1995). The c-Jun protein is overexpressed in ®broblast cells transformed by the Ras or Raf oncoproteins (Sistonen et al, 1989;Rapp et al, 1994b). It is therefore possible that the elevated levels of the c-Jun protein in cells expressing constitutive active Ras/Raf mediates the accumulation of the cyclin D1 protein.…”

Section: Constitutive Activation Of Ras or Raf Induces Cyclin D1 Overmentioning

confidence: 99%

Cell cycle targets of Ras/Raf signalling

1998

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The regulation of cell proliferation in multicellular organisms is a complex process, which is primarily regu-lated by external growth factors provided by surrounding cells. Once induced to proliferate, the passage through the mitotic cell cycle is directed by the components of the so called cell cycle machinery. Over the last years research on growth factor signaltransduction and the components of the cell cycle system has lead to a detailed knowledge of the mechanisms by which growth factors transmit their signals and of the relationship between the components of the cell cycle machinery. The remaining question how the growth factor mediated signal-transduction cascades couple with the cell cycle regulators has recently been a focus of interest.Keywords: Ras; Raf; cell cycleThe Ras GTP-binding protein and Raf kinases have a central role in transmitting growth factor-triggered signals. The Ras protein is an important e ector of growth factor receptors and activates di erent signaltransduction cascades (Daum et al., 1994;Avruch et al., 1994;Rodriguez Viciana et al., 1996;Symons, 1996). One of these is the Ras/Raf/Mek/Erk cascade (Daum et al., 1994). By direct interaction the Ras protein targets the Raf kinase to the plasma membrane where the catalytic activity of the kinase becomes activated. Subsequently Raf stimulates the Mek kinase by phosphorylation, which then phosphorylates and activates the Erk kinases. The Erk kinases shuttle into the nucleus and induce the activity of transcription factors. By employing constitutively active and dominant negative mutants of the Ras and Raf proteins it has been shown that the Ras/Raf signaltransduction cascade plays a crucial role in the regulation of cell proliferation by growth factors (Mulcahy et al

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“…GLUT1 messenger RNA indeed increases 3-4 days before morphological transformation and this increase is not correlated with the cell proliferation rate [21][22][23]. Transfection to rat fibroblast of activated ras or src oncogenes results in an elevation of the cytosolic concentration of mRNA responsible for the synthesis of glucose transporter [24].…”

Section: Biological Characteristics Of 18-fdgmentioning

confidence: 99%

Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose

Rigo¹,

Paulus²,

et al. 1996

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Abstract. Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and followup. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved.

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The cellular response to induction of the p21 c-Ha-ras oncoprotein includes stimulation of jun gene expression.

Cited by 107 publications

References 76 publications

Transformation by ras modifies AP1 composition and activity

Transformation by ras modifies AP1 composition and activity

Cell cycle targets of Ras/Raf signalling

Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose

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