12-O-tetradecanoylphorbol-13-acetate stimulates release of arachidonic acid, prostaglandin E2 and prostaglandin F2α from TPA nonproliferative variants of 3T3 cells

Butler‐Gralla, Edith; Taplitz, S J; Herschman, Harvey R.

doi:10.1016/s0006-291x(83)80135-1

Cited by 29 publications

(10 citation statements)

References 7 publications

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“…This is consistent with earlier observations that 3T3-TNR9 cells possess a phorbol ester binding on May 10, 2018 by guest http://mcb.asm.org/ Downloaded from activity and are able to respond to TPA with increases in glucose transport and arachidonic acid release (6,7,9). Thus, a lesion in some postreceptor step in the sequence of events leading to mitogenesis is likely to be responsible for the failure of 3T3-TNR9 cells to respond mitogenically to TPA.…”

Section: Discussionsupporting

confidence: 92%

“…Binding studies with whole cells, using isotopically labeled phorbol dibutyrate, suggested that the 3T3-TNR9 variant retains TPA "receptors" (6). TPA stimulates several aspects of the pleiotypic response in the nonproliferative variant, including glucose transport and arachidonic acid release, but is unable to stimulate, in the 3T3-TNR9 cells, the elevation of ornithine decarboxylase seen in the parental cells (8,9). In contrast, ornithine decarboxylase induction (as well as mitogenesis) occurs in both 3T3 and 3T3-TNR9 cells after exposure to serum. In an attempt to identify significant differences in the pathways of TPA-induced and EGF-induced mitogenesis which might be responsible for the TPA nonresponsiveness of the 3T3-TNR9 cells, we have analyzed some of the earliest phosphorylation events of the pleiotypic response in these cells.…”

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confidence: 99%

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Protein phosphorylation in a tetradecanoyl phorbol acetate-nonproliferative variant of 3T3 cells.

Bishop¹,

Martinez²,

Weber³

et al. 1985

Mol. Cell. Biol.

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The 3T3-TNR9 cell line is a variant of Swiss 3T3 cells which does not respond mitogenically to tumor promoters, but does respond mitogenically to epidermal growth factor, fibroblast growth factor, and serum. To elucidate differences between tumor promoters and polypeptide mitogens in the pathway(s) of mitogenesis which might be responsible for the nonresponsiveness of the 3T3-TNR9 cells, we have examined in these cells the early protein phosphorylation events known to be associated with mitogenesis in the parental 3T3 cells. We find that the 3T3-TNR9 cells display levels of tetradecanoyl phorbol acetate binding and of a calcium- and phospholipid-dependent protein kinase activity which are at least the equal of those seen in the parental 3T3 cells, implicating some postreceptor event in the nonmitogenic phenotype. In addition, we find that phosphorylation of the epidermal growth factor receptor and of 80-kDa and 22-kDa proteins, as well as the tyrosine phosphorylation of a 42-kDa protein, all proceed normally in the nonmitogenic variant, even though these phosphorylations must depend on the activation of different kinases. Thus, all these early phosphorylation reactions are intact in the 3T3-TNR9 cells. Although these phosphorylations may be necessary, they clearly are insufficient to trigger mitogenesis.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Protein phosphorylation in a tetradecanoyl phorbol acetate-nonproliferative variant of 3T3 cells.

Bishop¹,

Martinez²,

Weber³

et al. 1985

Mol. Cell. Biol.

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“…Forty-eight h later, the cultures were washed and treated with the PAHs or with DEP extract along with inducing ligands in medium containing 0.1% bovine serum albumin. Six h later, lipids were extracted from cell culture media and analyzed, as described previously (18,20), for total arachidonic acid-derived products, arachidonic acid, and prostaglandins. Briefly, total radioactivity in a portion of each lipid sample was determined to measure total arachidonic acid-derived products.…”

Section: Methodsmentioning

confidence: 99%

Diesel Exhaust Particle Extracts and Associated Polycyclic Aromatic Hydrocarbons Inhibit Cox-2-dependent Prostaglandin Synthesis in Murine Macrophages and Fibroblasts

Rudra-Ganguly¹,

Reddy²,

Kôrge

et al. 2002

Journal of Biological Chemistry

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Diesel exhaust particles (DEP) and their organic constituents modulate the immune system and exacerbate allergic airway inflammation. We investigated the role of DEP extract and associated polycyclic aromatic hydrocarbons (PAHs) on prostaglandin synthesis in endotoxin-activated murine macrophages and in mitogenstimulated fibroblasts. In both macrophages and fibroblasts, DEP extract, phenanthrene, anthracene, phenanthrenequinone, and ␤-napthoflavone inhibit prostaglandin production from endogenous arachidonic acid in response to ligand stimulation. However, DEP extract and PAHs do not block ligand induction of cyclooxygenase-2 (COX-2) protein, either in mitogenstimulated fibroblasts or endotoxin-treated macrophages. Release of total arachidonic acid and total lipid products is not reduced by DEP or PAHs following ligand stimulation of macrophages or fibroblasts. DEP extract and the PAHs inhibit the activity of purified COX-2 enzyme in vitro but do not inhibit COX-1 activity. Thus, DEP and PAHs do not affect ligand-induced COX-2 gene expression, phospholipase activation, or arachidonic acid release in macrophages and fibroblasts but exert their inhibitory effect on prostaglandin production by preferentially blocking COX-2 enzyme activity.

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“…3T3-TNR9 cells contain normal levels of functional PKC (6), and many of the early responses to TPA which occur in the parental 3T3 cells also occur in the variant, including phosphorylation of p80 and p22 (5; but see reference 3) and increased prostaglandin biosynthesis (10) and glucose transport (9). Furthermore, several genes that are specifically inducible by TPA in Swiss 3T3 cells are also expressed in the same inducible manner in 3T3-TNR9 cells (31).…”

Section: Methodsmentioning

confidence: 99%

“…TNR9 cells were derived from Swiss 3T3 cells on the basis of the inability to respond mitogenically to the tumor promoter 12-O-tetradecanoyl-13-acetate (TPA) (8), which is an analog of the normal signalling intermediate, diacylglycerol (4,15,16,18,21). 3T3-TNR9 cells contain normal levels of active protein kinase C (PKC) and respond to TPA stimulation like parental 3T3 cells with respect to most of the measured responses, including phosphorylation of p80 (5; but see reference 3), production of arachidonate metabolites, and elevation of glucose transport (9,10 boxylase, or DNA synthesis in these cells (9,19; G. L'Allemain, T. W. Sturgill, and M. J. Weber, submitted for publication). It has been reported recently that PKC is defectively down regulated in 3T3-TNR9 cells in response to long-term treatment with TPA (3).…”

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confidence: 99%

A Swiss 3T3 variant cell line resistant to the effects of tumor promoters cannot be transformed by src.

Nori¹,

Shawver²,

Weber³

1990

Mol. Cell. Biol.

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To study the relationship between oncogenesis by v-src and normal cellular signalling pathways, we determined the effects of v-src on 3T3-TNR9 cells, a Swiss 3T3 variant which does not respond mitogenically to tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We found that src was unable to transform these variant cells, whether the oncogene was introduced by infection with a murine retrovirus vector or by transfection with plasmid DNA. 3T3-TNR9 cells were not inherently resistant to transformation, since infection with similar recombinant retroviruses containing either v-ras or v-abl did induce transformation. Further analysis of Swiss 3T3 and 3T3-TNR9 cell populations infected with the v-src-containing retrovirus revealed that although the amount of v-src DNA in each was approximately the same, the level of the v-src message and protein and the overall level of phosphotyrosine expressed in the infected variants was much less than in infected parental cells. Cotransfection experiments using separate v-src and neo plasmids revealed a decrease in the number of G418-resistant colonies when transfections of TNR9 cells occurred in the presence of the src-containing plasmid, suggesting a growth inhibitory effect of v-src on 3T3-TNR9 cells, as has also been found for TPA itself. Since v-src cannot transform this variant cell line, which does not respond mitogenically to the protein kinase C agonist TPA, we suggest that src makes use of the protein kinase C pathway as part of its signalling activities.

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12-O-tetradecanoylphorbol-13-acetate stimulates release of arachidonic acid, prostaglandin E2 and prostaglandin F2α from TPA nonproliferative variants of 3T3 cells

Cited by 29 publications

References 7 publications

Protein phosphorylation in a tetradecanoyl phorbol acetate-nonproliferative variant of 3T3 cells.

Protein phosphorylation in a tetradecanoyl phorbol acetate-nonproliferative variant of 3T3 cells.

Diesel Exhaust Particle Extracts and Associated Polycyclic Aromatic Hydrocarbons Inhibit Cox-2-dependent Prostaglandin Synthesis in Murine Macrophages and Fibroblasts

A Swiss 3T3 variant cell line resistant to the effects of tumor promoters cannot be transformed by src.

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