ISSN:
1600-0625
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract The effect of epidermal growth factor (EGF) on the activity of ornithine decarboxylase (ODC) was evaluated and partially characterized in SV40-transformed, immortalized cultured human keratinocytes. It was observed that the addition of fresh complete medium to confluent cultures resulted in a 10-fold increase in ODC activity. Characterization of this activity using serum-free medium revealed that the increase in ODC activity was primarily due to the presence of EGF (10 ng/ml). A dose-dependent increase in ODC activity was observed when cultures were treated with EGF. Although near maximal induction occurred with EGF concentrations as low as 2.5–10 ng/ml, maximal induction of ODC (25-fold) occurred with an EGF concentration of 50 ng/ml. The peak time for ODC induction was 10 hours following the addition of EGF to keratinocyte cultures. The induction of ODC by EGF was inhibited by pretreatment of cultures with either cycloheximide or actinomycin D, suggesting that both protein synthesis and gene transcription are important in the FGF induction of ODC. EGF significantly increased the steady stale levels of ODC mRNA with a peak at 4 hours, preceding the peak in observed enzyme activity as expected. Pretreatment of cultures with retinoic acid (10−5–10−7M) significantly inhibited the induction of ODC by EGF. Retinoic acid decreased the steady-state levels of ODC mRNA. These data demonstrate that ODC is an enzyme that is induced by EGF in human keratinocytes; this induction probably involves both gene transcription and protein synthesis. Retinoic acid partially prevents the EGF induction of ornithine decarboxylase activity through a presently undefined mechanism(s), but appears to have effects that result in decreased ODC mRNA levels.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1600-0625.1993.tb00020.x
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