Epidermal growth factor induces Gadd45 (growth arrest and DNA damage inducible protein) expression in A431 cells

Epidermal growth factor (EGF) receptor over-expressing, p53-deficient A431 cells response to toxic dose of EGF by G1 arrest and apoptosis. Applying cD NA expression array technology we demonstrated that EGF increased the level s of Gadd45 mRNA. Northern blot and Western blot analyses confirmed that bo th Gadd45 mRNA and protein were increased. Concurrently half-lives of Gadd4 5 mRNA and protein also increased. Nuclear run-on experiments did not show a large increase of Gadd45 mRNA transcription rate. Gadd45 mRNA and protein started to increase after 1 h of EGF treatment and remained high for up to 10 h. We have also confirmed previous studies which showed that in EGF-sti mulated A431 cells p21(Cip1/Waf1) (cyclin-dependent kinase interacting prot ein 1) was up-regulated within the same time frame. Thus it appears that in addition to inducing G2 arrest by directly disrupting Cdc2/Cyclin B1 compl ex in genotoxic-stressed cells, Gadd45 may also participate in G1 arrest in growth factor overexposed cells. (C) 2001 Elsevier Science B.V. All rights reserved.