title: Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C.
abstract: cDNA clones representing genes whose expression is modulated by treatment with mitogens and tumor promoters were isolated and characterized. TPA-S1 corresponds to an mRNA species whose abundance was increased markedly within 1 h of exposure to the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), and TPA-R1 represents an mRNA that was decreased in TPA-treated cells. The induction of TPA-S1 was blocked by actinomycin D but was not affected by cycloheximide, and it was specific for phorbol esters with tumor-promoting activity. The role of protein kinase C in the induction of TPA-S1 is supported by the following lines of evidence. (i) Agents that activated protein kinase C (TPA, platelet-derived growth factor, and diacylglycerol) also increased TPA-S1 mRNA levels. (ii) A potent PKC inhibitor blocked the induction of TPA-S1. (iii) Down-regulation of PKC activity, by treatment of cells with TPA for 24 h, resulted in a loss of responsiveness to TPA-S1 induction by subsequent TPA treatment. DNA sequence analysis of TPA-S1 predicts a cysteine-rich, secreted protein with a molecular weight of 22.6 X 10(3) that exhibits homology with sequences representing a protein with human erythroid-potentiating activity and protease inhibitory activity.
authors: Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors: M D
authors: MD
authors: Johnson
authors: G M
authors: GM
authors: Housey
authors: P T
authors: PT
authors: Kirschmeier
authors: I B
authors: IB
authors: Weinstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology; D005809:Genes, Regulator / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*
chemical_list: D004075:Diglycerides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D003609:Dactinomycin; D004247:DNA; D003513:Cycloheximide; D011493:Protein Kinase C