Transient induction of ornithine decarboxylase mRNA in rat hepatoma cells treated with 12-O-tetradecanoylphorbol-13-acetate

Butler, Andrew C.; McDonald, Frances F.

doi:10.1016/0006-291x(87)91002-3

Cited by 13 publications

(4 citation statements)

References 20 publications

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“…Induction of ODC activity and mRNA by TPA appears uniformly reduced in transfectants (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) fold induction of activity; fig. 3, table 2) as compared to NIH3T3 cells fold induction of activity; fig 3, table 1).…”

Section: Odc Lability and Its Effect On Regulationmentioning

confidence: 99%

“…ODC mRNA levels, like those of the proto-oncogenes c-fos and c-myc, undergo a rapid but transient increase when quiescent cells are treated with serum [3,4] or 12-0-tetradecanoyl-phorbol-13-acetate (TPA) [3,5,6,7]. Furthermore, ODC mRNA is also subject to superinduction by simultaneous treatment of cells with mitogens and inhibitors of protein synthesis [3,4,8].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

1989

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To determine the genetic elements required for modulation of ornithine decarboxylase (ODC) activity in response to cell growth or treatment with serum or with tetradecanoyl phorbol acetate, ODCdeficient cells were transfected with a series of recombinant DNAs encoding mouse ODC. All of the transfected cells expressing an intact mouse ODC protein displayed regulation of ODC activity, including those expressing a construct deprived of all ODC-specific sequence information except the protein-coding region. ODC mRNA changed much less than enzymatic activity. A mutation of the protein-coding region that converted ODC from an unstable to a stable intracellular protein attenuated the regulatory response. We conclude that post-transcriptional events associated with ODC degradation dominate the response to these stimuli.

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Section: Odc Lability and Its Effect On Regulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

1989

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“…The potential importance of aberrant ODC expression to carcinogenesis is underscored by recent evidence suggesting that enforced overexpression of ODC may contribute directly to tumorigenesis [8,91. Regulation of ODC activity occurs by a variety of mechanisms, including transcription [ 10-1 21, translation [ I 31, and enzyme stability [141. However, evidence from several laboratories clearly indicates that induction of ODC activity by mitogenic stimuli or by phorbol-ester tumor promoters is directly correlated with increased levels of ODCtranscripts [4,7,15,16]. Furthermore, nuclear run-on experiments have demonstrated that increased levels of ODC mRNA in response to mitogenic stimuli may be accompanied by increased rates of ODC transcription in a cell-type-dependent and possibly mitogen-specific fashion [11,12,17].…”

Section: Introductionmentioning

confidence: 99%

“…Serum stimulation of ODC promoter in Rat2 fibroblasts. (A) Cells were transfected with plasmids pODClux1 (nt -1 156 t o +13), pODClux2 (nt -409 t o +13), or pODClux2AE (nt -92 to +13) and maintained in complete medium containing 10% FCS for16 h, when they were refed with low serum medium (DMEM plus 0.1 % FCS). At 42 h after transfection, half the dishes were refed with DMEM plus 20% FCS (hatched bars), while the other half received fresh DMEM plus 0.1% FCS (solid bars).…”

mentioning

confidence: 99%

Characterization of novel phorbol ester‐ and serum‐responsive sequences of the rat ornithine decarboxylase gene promoter

Mar

Kumar

Kang

et al. 1995

Molecular Carcinogenesis

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Ornithine decarboxylase (ODC), the key regulatory enzyme in mammalian polyamine biosynthesis, is rapidly induced by mitogens and tumor promoters. We used transient expression assays and DNA-protein binding studies to examine the regulation of ODC promoter activity by phorbol esters and serum growth factors. A fragment of the ODC 5' flanking region (nt-1156 to +13) was sufficient to confer 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive expression to a luciferase reporter gene when transfected into H35 cells. However, induction by TPA was not observed in Rat2 fibroblasts, although refeeding of serum-starved Rat2 cells with fresh serum-containing medium rapidly induced a fivefold to sixfold increase in ODC promoter activity, maximal about 8 h after refeeding. Deletion analysis demonstrated that several sequences contributed to basal ODC promoter activity but that nt -92 to +13 was sufficient for induction by TPA or by serum. This sequence lacked canonical TPA-responsive elements, and an activator protein-1 (AP-1) consensus oligonucleotide failed to compete effectively for proteins binding to this region. Two of four protein complexes observed by gel-shift analysis of nt -92 to +13 were competitively inhibited by wild-type but not mutant oligonucleotides encompassing a variant cyclic AMP-response element (CRE) (ODC nt -50 to -42); however, a consensus CRE did not compete. Mutagenesis of this site demonstrated that it contributes to basal expression of the ODC promoter but not to TPA or serum responsiveness. Thus, we conclude that the proximal ODC promoter (nt -92 to +13) responds to TPA and serum stimulation in a cell-type-specific manner that is not mediated by canonical AP-1 elements.

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Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C‐kinase‐deficient rat hepatoma cells

Butler

Cohn

Mar

et al. 1991

Journal Cellular Physiology

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Tumor-promoting phorbol esters and insulin produce similar effects in Reuber H35 rat hepatoma cell proliferation, including increased ornithine decarboxylase (ODC) enzyme activity, DNA synthesis, and mitogenesis. We investigated ODC mRNA accumulation in cells treated with either insulin or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Both agents caused rapid accumulation of ODC mRNA: for TPA, it was maximal 3 hr after treatment (4-6-fold greater than control cells) and returned quickly to control levels; for insulin, it was significantly longer, continuing to increase for at least 6 hr. Simultaneous treatment with TPA and insulin led to additive effects on ODC mRNA. Induction of ODC by TPA was blocked by down-regulation or inhibition of protein kinase C (PKC), consistent with a PKC-mediated mechanism. In contrast, PKC down-regulation had little effect on ODC induction by insulin. Furthermore, although both agents stimulated ribosomal S6 protein phosphorylation in cells containing normal amounts of PKC, the response to TPA was abolished in PKC-depleted cells; the effect of insulin was only slightly inhibited. TPA caused a rapid redistribution of essentially all of the PKC activity from the cytosolic to the membrane fraction of the cells, whereas insulin had no effect on PKC distribution. These results suggest that although insulin and TPA share some common cytoplasmic signalling pathways, their effects on phosphorylation of nuclear proteins and transcription of ODC may be mediated by distinct factors.

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Transient induction of ornithine decarboxylase mRNA in rat hepatoma cells treated with 12-O-tetradecanoylphorbol-13-acetate

Cited by 13 publications

References 20 publications

Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

Characterization of novel phorbol ester‐ and serum‐responsive sequences of the rat ornithine decarboxylase gene promoter

Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C‐kinase‐deficient rat hepatoma cells

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