Abstract
We made use of QNR cells transformed by a thermosensitive (tsNY68) strain of the Rous sarcoma virus (RSV) to compare the effect of p60v-src and serum in cultured nerve cells. In this system, both p60v-src heat inactivation and serum removal resulted in growth arrest in G1. In both cases, growth arrest was reversible since cell proliferation was rapidly re-induced following respectively p60v-src renaturation or serum re-addition. However, cells did not fully recover their ability to grow in soft agar, suggesting that, in contrast to the cell cycle machinery, the transforming capacities of these cells have been irreversibly altered. We found that p60v-src kinase activity prevented detachment from the substratum and cell death following serum removal. Thermal inactivation of p60v-src at restrictive temperature (41.5°C), but not serum removal, resulted in dramatic morphological changes, which occured 4 h after temperature shift up to 41.5°C. Later on, typical features of apoptotic cells could be observed. Cell death was greatly reduced by the caspase-3 inhibitor ZVAD.FMK, but not by the caspase-1 inhibitor Ac-YVAD.CHO. Together, these results suggested that p60v-src and serum factors act on distinct pathways, at least in part. In an attempt to identify the signalling pathways involved in the cell response to p60v-src down regulation, we found that Erk and Rac were rapidly inactivated following temperature shift up to 41.5°C. Thus, the combined effects of p60v-src and serum factors on the cytoskeleton dynamics and the apoptosis machinery are essential for full neoplastic transformation of neuroretina cells.
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Acknowledgements
Mrs J Bernaud has to be specially acknowledged for her help for FACS analysis. We thank Dr A Srinavasan, Dr J Collard and Dr S Taylor for plasmids and antibodies. This work has been supported by grants from Association pour la lutte Contre le Cancer (ARC), Ligue Nationale Contre le Cancer (comité du Rhône), Fondation pour la Recherche Médicale, Université Claude Bernard and Association Retina France. AA and SO are recipients of fellowships from the ARC and the Ministère de l'éducation et de la recherche (France), J-R Schmitt was recipient from fellowships from the Ligue Nationale Contre le Cancer and the ARC.
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Aouacheria, A., Ory, S., Schmitt, JR. et al. p60v-src and serum control cell shape and apoptosis via distinct pathways in quail neuroretina cells. Oncogene 21, 1171–1186 (2002). https://doi.org/10.1038/sj.onc.1205170
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DOI: https://doi.org/10.1038/sj.onc.1205170
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