Mechanisms involved in ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate, a potent mouse skin tumor promoter and an activator of protein kinase C.
ODC, the first enzyme in mammalian polyamine biosynthesis, is rapidly induced in response to a wide variety of growth stimuli. However, there is no single mechanism which may explain the rapid turnover of ODC activity. ODC activity has been shown to be regulated at the level of synthesis and degradation, and also by post-translational modifications and an interaction with macromolecules. Our results indicate that TPA-induced ODC activity is regulated at the transcriptional level. An initial signal in ODC induction by TPA is not clear. We have suggested that TPA-increased accumulation of epidermal prostaglandins is required, but not sufficient, for ODC induction by TPA. Others have suggested the role of lipoxygenase product(s) in ODC induction. The role of the microtubule-containing system in regulation of ODC induction has been shown. The involvement of cyclic nucleotides in ODC induction by TPA is controversial. Also, generation of free radicals appears to be involved in ODC induction by TPA. Data summarized in this chapter indicate that activation of PKC may be an initial step in ODC induction by TPA.
Verma
A K
AK
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Hsieh
J T
JT
Pong
R C
RC
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000494:pharmacology
D012333:RNA, Messenger; D011493:Protein Kinase C; D010738:Type C Phospholipases; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate