Induction of the human ARF protein by serum starvation

The ARF protein encoded by the alternative transcript of the INK4a gene inh ibits cell growth by stabilization of p53. ARF is induced by activated onco genes sucll as c-myc, E1A and E2F-1. We show here that ARF protein expressi on is also induced by serum deprivation in the human tumor cell line MDA-MB -157 and in the SV40 large T-immortalized keratinocyte line Rhek. This incr ease of expression was reversed by the addition of serum. ARF mRNA levels a lso increased after serum starvation, suggesting that ARI: upregulation is mediated, at least in part, by increased transcription and/or mRNA stabilit y. These results indicate that ARF responds not only to oncogenic hyper-pro liferative signals but also to suboptimal growth conditions.