Effect of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) on the growth inhibitory and increased phosphatidylinositol (PI) responses induced by epidermal growth factor (EGF) in A431 cells

Smith, Kathryn B.; Losonczy, Ilona; Sahai, Atul; Pannerselvam, Mounanandham; Fehnel, Paula; Salomon, David

doi:10.1002/jcp.1041170113

Cited by 69 publications

(29 citation statements)

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“…However, the inhibitory effect of TPA on A431 cell growth was rather weak. The result is compatible with the pre vious report that demonstrated, a weak inhibi tion of A431 cell growth by TPA (8). It has generally been accepted that ODC induction is closely related to cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…We have shown that protein kinase C plays an essential role in TPA-evoked ODC induction in mouse skin and epidermal cells (5 -7) , targets of skin tumor promotion by this agent. It has been reported that TPA inhibits the growth of A431 human epidermoid carci noma cells (8). To examine the role of protein kinase C in ODC induction in the cells whose growth is inhibited by TPA, we examined the effects of TPA and protein kinase C activators on serum factor(s)-caused ODC induction in A431 cells and found that ODC induction is negatively regulated by the protein kinase C system in these cells.…”

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confidence: 99%

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Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

et al. 1991

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Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more promi nent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-0 retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol-13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down-regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

et al. 1991

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“…Effects of Specific Inhibitors of Signal Transducers on a a 1 -Adrenergic Agonist Phenylephrine-Induced ERK Isoform Phosphorylation in the Presence of EGF The effects of a 1 -adrerenergic agonists on induction of ERK1/2 phosphorylation by 20 ng/ml EGF were investigated using the a 1 -adrenergic agonist phenylephrine (10 Ϫ6 M 36) ) and 12-O-tetradecanoylphorbol-13-acetate (phorbol ester, TPA 37) ). When hepatocytes were stimulated with EGF in the presence of phenylephrine (10 Ϫ6 M), and/or TPA (10 Ϫ7 M), significant potentiation of ERK2 phosphorylation was not observed when compared with EGF (20 ng/ml) alone (Fig.…”

Section: Effect Of Specific Inhibitors Of Signal Transducers Onmentioning

confidence: 99%

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Moteki

Kimura

Ogihara

2011

Biological & Pharmaceutical Bulletin

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Epidermal growth factor (EGF) is well recognized as a potent mitogen, and appears to trigger liver regeneration after partial hepatectomy or after acute liver cell necrosis caused by chemicals in vivo. [1][2][3][4] The response of adult rat hepatocytes to EGF has also been extensively investigated with respect to DNA synthesis and proliferation in vitro. EGF is now known to be a potent hepatocyte mitogen and induces multiple biological activities in a wide variety of cell types. [5][6][7][8] More recently, we reported that EGF rapidly stimulates hepatocyte DNA synthesis and proliferation during short-term (e.g., 4 h) culture.9) In addition, the hepatocyte DNA synthesis and proliferation induced by EGF was inhibited depending on the initial plating density. Furthermore, we found that EGF-induced hepatocyte DNA synthesis and proliferation were potentiated by b 2 -adrenergic agonists. 9)The signal transduction pathways activated in response to EGF in hepatocytes and other cell types are now more clearly understood. [10][11][12] Using specific inhibitors of signal transducers, we pharmacologically demonstrated that EGF-receptor tyrosine kinase and ribosomal p70 S6 kinase activities, but not phosphoinositide 3-kinase (PI3K), are essential for EGFinduced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. 9) PI3K is considered to be involved in hepatocyte growth factor (HGF) signal transduction. 13)In addition, extracellular-signal regulated kinase (ERK)1/2, also known as mitogen-activated protein kinase (p42/44 MAPK), is now known to be activated in response to a large number of mitogenic stimuli, and this enzyme is a key participant in the response to various growth factors and cytokines.14,15) In order to better understand the EGF-mediated signaling pathway, we investigated whether activation of the ERK isoforms, ERK1 and ERK2, is involved in EGFinduced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.Catecholamines (e.g., norepinephrine and its analogs) have been shown to be involved in the regulation of liver function (e.g., lipid metabolism, carbohydrate metabolism and cell growth). There are several types of catecholamine receptors, b 1 -and b 2 -receptors, that stimulate adenylate cyclase (AC), while a 2 -receptor inhibits its phosphorylation. 5,16) a 1 -Receptor is involved in phospholipase C activation and subsequent increases in inositolphosphate turnover and diacylglycerol production.17,18) However, some investigators have reported that a 1 -and b-adrenergic responses are involved in adrenergic regulation of carbohydrate metabolism in the liver of normal adult rats and in cultured hepatocytes. 19,20) There are few studies regarding the adrenergic regulation of ERK1/2 phosphorylation induced by growth factors in liver cells. Therefore, in the present study, we examined whether a 1 -, a 2 -and b 2 -adrenergic agonists can modulate EGF-induced ERK1/2 isoform activities. The physiological significance of crosstalk between the EGF pathway and a 1 -, a 2 -and...

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“…Fetal calf serum may activate protein kinase C (Moolenaar et al 1981;1983) and so desensitization of receptors may occur which alters the contractile response. TPA may inhibit diacylglycerol formation by epidermal growth factor (Smith, Losonczy, Sahai, Pannerselvam, Fehnel & Salomon, 1983) and TPA may attenuate the stimulation of Na+-H+ exchange by epidermal growth factor (Whiteley, Cassel, Zhuang & Glaser, 1984). Capogrossi et at.…”

Section: K T Macleod and S E Hardingmentioning

confidence: 99%

Effects of phorbol ester on contraction, intracellular pH and intracellular Ca2+ in isolated mammalian ventricular myocytes.

MacLeod

Harding

1991

The Journal of Physiology

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SUMMARY1. We have investigated the actions of certain phorbol esters on the intracellular pH, intracellular Ca2+ and contractility of isolated rat and guinea-pig cardiac myocytes. Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and intracellular Ca2+ was measured using Fura-2.2. Application of the phorbol ester 12-0-tetradecanoylphorbol 13-acetate (also called phorbol 12-myristate 13-acetate) (TPA) (which activates protein kinase C) to rat cardiac myocytes significantly increased cell shortening by 116 + 34% (n = 8) (p < 002). The rate of change of cell length during contraction (i.e. + dL/dt) increased from 67-2 + 817 gim/s to 127-7 + 14-1 gm/s (n = 7). The rate of change of cell length during relaxation (-dL/dt) increased from 55-8 + 7X4 gm/s to 1 18-9 + 1241 gcm/s (n = 7). Time to peak shortening was unchanged.3. Application of 4a-phorbol 12,13-didecanoate, which does not activate protein kinase C, did not affect rat myocyte contractility. An insignificant decrease in contractility (by 7-5 + 7'5%) was observed (n = 5). The positive inotropic effect of TPA may therefore be evoked through an activation of protein kinase C.4. In rat myocytes we have measured the changes of pHi and contractility (cell shortening) during an alkalosis and acidosis induced by exposure to and subsequent removal of NH4Cl both in the presence and absence of TPA. Recovery times from an acid load were significantly (p < 005) enhanced by 1541+ 69 % (n = 13) in the presence of TPA. Recovery times of cell shortening were also more rapid (p < 005) by an average of 59-1 + 10-6 % (n = 5) in the presence of TPA. Recovery times were unchanged in the presence of 4-phorbol 12,13-didecanoate (wirhich does not activate protein kinase C).5. Since pHi recovery of an isolated myocyte from an acid load is partially inhibited by the presence of 1 mM-amiloride and inhibited by removing extracellular Na+ then it is suggested that, like pHi regulation in sheep heart Purkinje fibres, pH1 recovery in rat cardiac ventricular myocytes is mainly through sarcolemmal Na+-H+ exchange. We suggest that in the presence of TPA the Na+-H+ exchange is stimulated. (diastolic) [Ca21]. Fura-2 ratios increased by 21+4%(n = 5). We conclude that some of the positive inotropic effect produced by phorbol esters which activate protein kinase C is caused by an increase in systolic Ca2+.

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Effect of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) on the growth inhibitory and increased phosphatidylinositol (PI) responses induced by epidermal growth factor (EGF) in A431 cells

Cited by 69 publications

References 42 publications

Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

Inhibitory Regulation of Serum Factor(s)-Caused Ornithine Decarboxylase Induction by the Protein Kinase C System in A431 Human Epidermoid Carcinoma Cells.

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Effects of phorbol ester on contraction, intracellular pH and intracellular Ca2+ in isolated mammalian ventricular myocytes.

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