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To investigate the role of oncogene activation in the pathogenesis of malignant tumors, we have studied the tumorigenic and metastatic properties of NIH/3T3 secondary transfectants (designated A51) containing an activated c-Ha-ras-1 gene derived from the human T24 bladder carcinoma cell line and compared them with untransfected NIH/3T3 cells. Whereas subcutaneous implantation of NIH/3T3 cells in the supraclavicular region produced palpable tumors that failed to metastasize, NIH/3T3 cells inoculated in the footpad gave rise to malignant tumors that metastasized to the lung. Under identical conditions and irrespective of the site of implantation, A51 cells formed rapidly growing primary tumors that produced pulmonary metastases. In an assay for experimental metastasis, intravenously injected NIH/3T3 cells gave rise to pulmonary nodules only at high cell inocula and in long-term survivors (90 days after injection). In contrast, A51 cells formed multiple lung tumor colonies detectable 14 days after injection. These results indicate that "normal" untransfected NIH/3T3 cultures contain subpopulations of cells that express malignant properties and that transfection of NIH/3T3 cells with activated c-Ha-ras-1 accelerates formation of metastases.
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
January 1989,
Cellular signalling,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
June 1988,
Cancer research,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
September 1987,
Proceedings of the National Academy of Sciences of the United States of America,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
October 1992,
Experimental cell research,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
April 1989,
The American journal of physiology,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
January 1985,
Molecular and cellular biology,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
January 1994,
Oncology research,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
February 1993,
Cancer research,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
October 1994,
Molecular and cellular biochemistry,
R G Greig, and
T P Koestler, and
D L Trainer, and
S P Corwin, and
L Miles, and
T Kline, and
R Sweet, and
S Yokoyama, and
G Poste
December 1994,
Oncogene,
