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E2F1 Messenger RNA Is Destabilized in Response to a Growth Inhibitor in Normal Human Keratinocytes but not in a Squamous Carcinoma Cell Line¹

Epithelial Pathobiology Group, Centre For Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia, 4102

Keratinocyte growth arrest is characterized by a reduction in the activity and expression of E2F1. Here, we examine the role posttranscriptional processing plays in the down-regulation of E2F1 during keratinocyte growth arrest. E2F1 mRNA levels were undetectable within 8 h of exposure to the protein kinase C activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Assays of transcript stability indicated that, in untreated keratinocytes, the t_1/2 of E2F1 mRNA was 6.1 h and, in TPA-treated cells, it was 1.7 h. This destabilization was protein synthesis-dependent. In contrast, a growth inhibitor-resistant carcinoma cell line, SCC25, has a very stable E2F1 half-life that was only moderately reduced following TPA treatment. These data demonstrate that the initiation of keratinocyte growth arrest is associated with a rapid destabilization of E2F1 mRNA. These data are consistent with the proposition that inactivation of the posttranscriptional processing of important growth regulatory genes (e.g., E2F1) may contribute to neoplasia.

¹ This work was supported by Queensland Cancer Fund Grant 95/QCFN003G, Australian Research Council Grant 96/ARCS016G. The Garnett Passe and Rodney Williams Memorial Foundation, and the Princess Alexandra Hospital Research Foundation. A. J. D. is funded by a National Health and Medical Research Council Predoctoral Fellowship.

² To whom requests for reprints should be addressed, at University of Queensland Department of Medicine, Princess Alexandra Hospital, Ipswich Road, Brisbane, Australia, 4102. Phone: 61 7 3240 5936; Fax: 61 7 3240 5946; E-mail: NSaunders@medicine.pa.uq.edu.au.

Received 1/15/98. Accepted 3/ 3/98.

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