Transformed NIH 3T3 cells expressing human melanoma N-ras oncogene metastasize to lymph node in nude mice

1989 ◽  
Vol 7 (4) ◽  
pp. 391-403 ◽  
Author(s):  
J. Jouanneau ◽  
M. Longuet ◽  
S. Bertrand
Keyword(s):  
Lymph Node ◽  
Nude Mice ◽  
Human Melanoma ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Depletion of c-myc with specific antisense sequences reverses the transformed phenotype in ras oncogene-transformed NIH 3T3 cells.

1991 ◽  
Vol 11 (7) ◽  
pp. 3699-3710 ◽  
Author(s):  
M D Sklar ◽  
E Thompson ◽  
M J Welsh ◽  
M Liebert ◽  
J Harney ◽  
...  
Keyword(s):  
Nude Mice ◽  
Growth Rates ◽  
Monolayer Culture ◽  
Soft Agar ◽  
Ras Oncogene ◽  
Minimum Level ◽  
3T3 Cells ◽  
Sense Orientation ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ras oncogene-transformed NIH 3T3 cells expressing glucocorticoid-inducible antisense c-myc cDNA transcripts at levels sufficient to deplete c-myc protein lost their transformed morphology and the ability to grow in soft agar; their ability to form tumors in nude mice was also impaired. These changes were dependent on the continuous expression of the antisense sequences. No major effects on plating efficiencies, growth rates in monolayer culture, or immortalization were observed in the revertant cells, indicating that the observed effects were not a toxic consequence of c-myc protein depletion. Transfection with the same vector expressing c-myc in the sense orientation or other control vectors had no effect on transformation. These results suggest that a certain minimum level of expression of c-myc is required for the maintenance of ras transformation in NIH 3T3 cells.

Depletion of c-myc with specific antisense sequences reverses the transformed phenotype in ras oncogene-transformed NIH 3T3 cells

1991 ◽  
Vol 11 (7) ◽  
pp. 3699-3710
Author(s):  
M D Sklar ◽  
E Thompson ◽  
M J Welsh ◽  
M Liebert ◽  
J Harney ◽  
...  
Keyword(s):  
Nude Mice ◽  
Growth Rates ◽  
Monolayer Culture ◽  
Soft Agar ◽  
Ras Oncogene ◽  
Minimum Level ◽  
3T3 Cells ◽  
Sense Orientation ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ras oncogene-transformed NIH 3T3 cells expressing glucocorticoid-inducible antisense c-myc cDNA transcripts at levels sufficient to deplete c-myc protein lost their transformed morphology and the ability to grow in soft agar; their ability to form tumors in nude mice was also impaired. These changes were dependent on the continuous expression of the antisense sequences. No major effects on plating efficiencies, growth rates in monolayer culture, or immortalization were observed in the revertant cells, indicating that the observed effects were not a toxic consequence of c-myc protein depletion. Transfection with the same vector expressing c-myc in the sense orientation or other control vectors had no effect on transformation. These results suggest that a certain minimum level of expression of c-myc is required for the maintenance of ras transformation in NIH 3T3 cells.

Metabolism of n-6 fatty acids by NIH-3T3 cells transfected with the ras oncogene

1994 ◽  
Vol 139 (1) ◽  
pp. 71-81 ◽  
Author(s):  
R. J. de Antueno ◽  
R. C. Cantrill ◽  
Y-S. Huang ◽  
G. W. Ells ◽  
M. Elliot ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Alpha B-crystallin expression in mouse NIH 3T3 fibroblasts: glucocorticoid responsiveness and involvement in thermal protection.

1993 ◽  
Vol 13 (3) ◽  
pp. 1824-1835 ◽  
Author(s):  
A Aoyama ◽  
E Fröhli ◽  
R Schäfer ◽  
R Klemenz
Keyword(s):  
Heat Shock ◽  
Thermal Protection ◽  
Cell Clone ◽  
Ectopic Expression ◽  
Small Heat Shock Protein ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
3T3 Fibroblasts ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

alpha B-crystallin, a major soluble protein of vertebrate eye lenses, is a small heat shock protein which transiently accumulates in response to heat shock and other kinds of stress in mouse NIH 3T3 fibroblasts. Ectopic expression of an alpha B-crystallin cDNA clone renders NIH 3T3 cells thermoresistant. alpha B-crystallin accumulates in response to the synthetic glucocorticoid hormone dexamethasone. Dexamethasone-treated NIH 3T3 cells become thermoresistant to the same extent as they accumulate alpha B-crystallin. A cell clone in which alpha B-crystallin is superinduced upon heat shock acquires augmented thermotolerance. Expression of the ras oncogene causes a rapid but transient accumulation of alpha B-crystallin within 1 day. Later, sustained ras oncogene expression suppresses the dexamethasone-mediated alpha B-crystallin accumulation. Thus, oncogenic transformation triggered by the ras oncogene interferes with hormone-mediated accumulation of alpha B-crystallin and concomitant acquisition of thermoresistance. Other known heat shock proteins do not accumulate in response to ectopic alpha B-crystallin expression or to dexamethasone treatment. These results indicate that alpha B-crystallin can protect NIH 3T3 fibroblasts from thermal shock.

scholarly journals NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice.

1985 ◽  
Vol 5 (1) ◽  
pp. 259-262 ◽  
Author(s):  
U P Thorgeirsson ◽  
T Turpeenniemi-Hujanen ◽  
J E Williams ◽  
E H Westin ◽  
C A Heilman ◽  
...  
Keyword(s):  
Nude Mice ◽  
Dna Sequences ◽  
Immune Cell ◽  
Human Tumor ◽  
3T3 Cells ◽  
Metastatic Phenotype ◽  
Ras Oncogenes ◽  
Nih 3T3 ◽  
Tumor Dna ◽  
Nih 3T3 Cells

NIH/3T3 cells transfected with DNA from malignant human tumors produced experimental and spontaneous metastases in nude mice. In contrast, parent or spontaneously transformed NIH/3T3 cells failed to metastasize. The transfected clones contained either activated c-Harvey-ras or N-ras oncogenes. A representative clone (T71-17SA2) which was used to assess selected cellular and host factors relevant to the metastatic process produced lung metastases in 100% of the NIH nude mice recipients, secreted augmented levels of type IV collagenase, and invaded human amnion basement membrane in vitro. Expression of the metastatic phenotype was not related to decreased sensitivity to natural killer cells or macrophage-mediated cytotoxicity. Analysis of the cellular DNA from the T71-17SA2 transfectant and its corresponding metastases, both of which contained activated N-ras oncogenes, revealed a twofold increase in the N-ras-specific DNA sequences in the metastatic cells. Thus, transfection with human tumor DNA containing activated ras oncogenes can induce the complete metastatic phenotype in NIH/3T3 cells by a mechanism apparently unrelated to immune cell killing.

Identifying the factors and signal pathways necessary for anchorage-independent growth of Ha-ras oncogene-transformed NIH/3T3 cells

Life Sciences ◽  
2003 ◽  
Vol 73 (10) ◽  
pp. 1265-1274 ◽  
Author(s):  
Tsuey-Yu Chang ◽  
Wen-Jiuan Tsai ◽  
Chao-Kai Chou ◽  
Nan-Haw Chow ◽  
Tzeng-Horng Leu ◽  
...  
Keyword(s):  
Signal Pathways ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
Anchorage Independent Growth ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Mutants of the RNA-dependent protein kinase (PKR) lacking double-stranded RNA binding domain I can act as transdominant inhibitors and induce malignant transformation.

1995 ◽  
Vol 15 (6) ◽  
pp. 3138-3146 ◽  
Author(s):  
G N Barber ◽  
M Wambach ◽  
S Thompson ◽  
R Jagus ◽  
M G Katze
Keyword(s):  
Malignant Transformation ◽  
Nude Mice ◽  
Rna Binding ◽  
Critical Role ◽  
Point Mutations ◽  
Dominant Negative ◽  
3T3 Cells ◽  
Double Stranded Rna ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Recently we reported that introduction of catalytically inactive PKR molecules into NIH 3T3 cells causes malignant transformation and the development of tumors in nude mice. We have proposed that PKR may be a tumor suppressor gene possibly because of its translational inhibitory properties. We have now designed and characterized a number of PKR mutants encoding proteins that retain their catalytic competence but are mutated in their regulatory double-stranded RNA (dsRNA) binding domains (RBDs). RNA binding analysis revealed that PKR proteins either lacking or with point mutations in the first RBD (RBD-1) bound negligible amounts of dsRNA activator or adenovirus VAI RNA inhibitor. Despite the lack of binding, such variants remained functionally competent but were much less active than wild-type PKR. PKR variants completely lacking RBD-1 were largely unresponsive to dsRNA in activation assays but could be activated by heparin. To complement these studies, we evaluated the effects of point mutations in RBD-1 or the removal of either RBD-1 or RBD-2 on the proliferation rate of mouse 3T3 cells. We were unsuccessful at isolating stably transformed cells expressing RBD-1 point mutants or RBD-2-minus mutants. In contrast, NIH 3T3 cells, which constitutively expressed PKR proteins that lacked RBD-1, were selected. These cells displayed a transformed phenotype and caused tumors after inoculation in nude mice. Further, levels of endogenous eIF-2 alpha phosphorylation in RBD-1-minus cell lines were reduced, suggesting that such mutants act in a dominant negative manner to inhibit the function of endogenous PKR. These results emphasize the importance of RBD-1 in PKR control of cell growth and provide additional evidence for the critical role played by PKR in the regulation of malignant transformation.

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