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Differential sensitivity to pertussis toxin of 3T3 cells transformed with different oncogenes
1Rhône-Poulenc Santé, Centre de Recherches de Vitry, Vitry-sur-Seine, France.
Abstract:
Pertussis toxin (PT), which blocks the activity of several G-proteins, has been found to exert a marked inhibitory effect on the DNA synthesis induced in 3T3 cells by serum or growth factors. 3T3 cells transformed with human c-ras oncogenes (Ha-ras, Ki-ras, N-ras) or with src, an oncogene coding for a protein kinase, have lost sensitivity to growth control by PT, even though substrates for PT can still be ADP-ribosylated in vivo. In contrast, 3T3 cells transformed with the SV40 virus behave like normal untransformed cells with respect to the ability of PT to decrease their growth rate. Oncogenes can thus likely be classified either as 'responders' or 'non-responders' to PT.
Insights
Pertussis toxin (PT) inhibits DNA synthesis in normal cells but not in cells with certain oncogenes. This suggests oncogenes can be classified as PT
Area of Science:
- Cell biology
- Molecular oncology
- Signal transduction
Background:
- Pertussis toxin (PT) inhibits G-protein activity, affecting DNA synthesis in normal cells.
- Cellular transformation by oncogenes can alter growth factor sensitivity.
Purpose of the Study:
- To investigate the effect of PT on DNA synthesis in oncogene-transformed cells.
- To determine if oncogene transformation confers resistance to PT-mediated growth inhibition.
Main Methods:
- Utilized 3T3 cells, both normal and transformed with various oncogenes (Ha-ras, Ki-ras, N-ras, src, SV40).
- Assessed DNA synthesis inhibition by PT in response to serum or growth factors.
- Confirmed PT substrate ADP-ribosylation in vivo in transformed cells.
Main Results:
- Normal 3T3 cells showed inhibited DNA synthesis upon PT treatment.
- Cells transformed with ras or src oncogenes lost sensitivity to PT's inhibitory effect on DNA synthesis.
- SV40-transformed cells retained sensitivity to PT, similar to normal cells.
Conclusions:
- Oncogene transformation, particularly by ras and src, can lead to PT resistance.
- Cells can be classified as 'responders' or 'non-responders' to PT based on oncogene status.
- This differential response highlights distinct signaling pathways affected by different oncogenes.