CELL-GROWTH INHIBITION BY PROSTAGLANDIN-A(2) RESULTS IN ELEVATED EXPRESSION OF GADD153 MESSENGER-RNA

Treatment of Hela cells with prostaglandin A2 (PGA2) resulted in a marked inhibition of cell proliferation which was associated with a significant induction of gadd153 mRNA, a member of a novel class of genes associated with growth arrest and DNA damage. Induction of gadd153 mRNA was specific to prostaglandins capable of arresting cell growth and was dose-dependent with the maximum effect seen at 36 μM PGA2. Induction was rapid, occurring within 2-4 h and reaching a maximum by 8 h. These effects were reversible as removal of PGA2 resulted in a rapid decline in gadd153 mRNA levels coincident with resumption of cell growth. PGA2 induction of gadd153 mRNA was completely prevented by the presence of actinomycin D at a concentration sufficient to block transcription and was partially inhibited (50%) by the protein synthesis inhibitor cycloheximide. The presence of the protein kinase inhibitor 2-aminopurine decreased the PGA2 induction of gadd153 mRNA by greater than 90%, suggesting that cellular kinases play a role in the induction of gadd153 by PGA2. Thus PGA2-mediated growth arrest provides a useful model to further define the role of gadd153 in the negative control of cell growth. © 1992.