Cell growth inhibition by prostaglandin A2 results in elevated expression of gadd153 mRNA.
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 microM 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.
Choi
A M
AM
Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224.
Fargnoli
J
J
Carlson
S G
SG
Holbrook
N J
NJ
D015075:2-Aminopurine / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011454:Prostaglandins A / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*
D011454:Prostaglandins A; D012333:RNA, Messenger; D003609:Dactinomycin; D015075:2-Aminopurine; D003513:Cycloheximide; C100008:prostaglandin A2