Oncogenic mutant of Gα12 stimulates cell proliferation through cycloxygenase-2 signaling pathway

Dermott, Jonathan M.; Reddy, MV Ramana; Onésime, Djamila; Reddy, E. Premkumar; Dhanasekaran, N.

doi:10.1038/sj.onc.1203345

Cited by 28 publications

(29 citation statements)

References 26 publications

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“…Therefore, G 12 and G q play important roles in ET-1-induced AA release. These results are consistent with the previous report, which demonstrated that the GTPase-deficient activated mutant of G 12 stimulates AA release in NIH 3T3 cells (Dermott et al, 1999). ET-1-induced AA release was not inhibited completely by G 12 G228A in this study (Fig.…”

Section: Discussionsupporting

confidence: 83%

Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor

Kawanabe

Nozaki²,

Hashimoto³

et al. 2003

Mol Pharmacol

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Endothelin-1 (ET-1) activates two types of Ca 2ϩ -permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca 2ϩ channel (SOCC) in Chinese hamster ovary cells expressing endothelin A receptors (CHO-ET A R). These channels can be distinguished by their sensitivity to Ca 2ϩ channel blockers 1- [385][386][387][388] ) ET A R (CHO-SerET A R), each of which is coupled with G q or G s /G 12 , respectively. In CHOSerET A R, a dominant-negative mutant of G 12 inhibited AA release. SK&F 96365 inhibited ET-1-induced AA release in CHO-ET A R⌬385, whereas LOE 908 inhibited it in CHO-SerET A R. These results indicate the following: 1) ET-1-induced AA release depends on Ca 2ϩ influx through NSCC-1, NSCC-2, and SOCC in CHO-ET A R; 2) G q and G 12 mediate AA release through ET A R in CHO cells; and 3) PI3K is involved in ET-1-induced AA release, which depends on NSCC-2 and SOCC.The release of arachidonic acid (AA) from the membrane lipids is catalyzed by phospholipase A 2 (PLA 2 ) in mammalian cells (Dennis, 1997). Hormones and growth factors including endothelin-1 (ET-1) stringently regulate PLA 2 activity (Dennis, 1997; Leslie, 1997;Trevisi et al., 2002). AA is converted into other biologically active metabolites such as leukotrienes, lipoxins, prostaglandins, and thromboxanes by different enzymes. These metabolites seem to play significant roles in several important processes, including vascular contraction and cell growth (Gong et al., 1995;Anderson et al., 1997). Previous reports indicate that the key enzyme responsible for agonist-induced AA release is cytosolic PLA 2 (cPLA 2 ) (Lin et al., 1992;Roshak et al., 1994). ET-1 also induces AA release through cPLA 2 activation (Trevisi et al., 2002). cPLA 2 is a cytosolic 85-kDa Ca 2ϩ -dependent PLA 2 and is activated by both an increase in intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) and Ser-505 phosphorylation by mitogen-activated protein kinase or protein kinase C (Leslie, 1997). Extracellular Ca 2ϩ influx plays critical roles in the ET-1-induced AA release (Stanimirovic et al., 1994;Wu-Wong et al., 1996)

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Section: Discussionsupporting

confidence: 83%

Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor

Kawanabe

Nozaki²,

Hashimoto³

et al. 2003

Mol Pharmacol

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“…In contrast, aspirin acts as nonspecific COX inhibitor; at 10 mM it inhibits COX-1 while at a concentration higher than 100 mM inhibits also COX-2 (Dermott et al, 1999). In our experiments, aspirin at the inhibitory concentrations for COX-1 (2.5 and 5 mg ml À1 ) did not exhibit any effect on HTR-IR cell proliferation.…”

Section: Discussioncontrasting

confidence: 61%

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

et al. 2003

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Two isoforms of cyclooxygenase (COX) participate in growth control; COX-1 is constitutively expressed in most cells, and COX-2 is an inducible enzyme in response to cellular stimuli. An induction of COX-2 found in neoplastic tissues results in increased cell growth, inhibition of apoptosis, activation of angiogenesis, and decreased immune responsiveness. Although both COX-1 and COX-2 inhibitors are suppressors of cell proliferation and appear to be chemopreventive agents for tumorigenesis, the molecular mechanisms mediating antiproliferative effect of COX inhibitors are still not well defined. This study contrasts and compares the effects of aspirin and celecoxib, inhibitors of COX-1 and COX-2, in rat hepatoma HTC-IR cells. The following were assessed: cell proliferation and apoptosis, ornithine decarboxylase (ODC) activity, and pattern expression of three immediate-early genes, c-myc, Egr-1, and c-fos. We have shown that the treatment of hepatocytes in vitro with the selective COX-2 inhibitor, celecoxib, was associated with induction of apoptosis and complete inhibition of cellular proliferation. Aspirin exhibited a small antiproliferative effect that was not associated with apoptosis. Treatment with celecoxib produced dose-and time-dependent decrease in ODC activity. In addition, at higher drug concentration the decrease in ODC activity was greater in proliferating than in resting cells. Much lesser inhibitory effect on ODC activity was observed in aspirin-treated cells. The two COX inhibitors did not change c-myc expression, significantly decreased the expression of Egr-1, and differentially altered expression of c-fos; aspirin did not change, but celecoxib dramatically decreased the levels of c-fos-mRNA. Our study revealed that celecoxib and aspirin share the ability to inhibit ODC activity and alter the pattern of immediate-early gene expression. It seems that some of the observed effects are likely to be related to COX-independent pathways. The precise mechanisms of action of COX inhibitors should be defined before using these drugs for cancer chemopreventive therapy.

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“…In addition, there is substantial evidence that Ga 12/13 proteins mediate signaling pathways involved in cell growth and tumorigenesis (Chan et al, 1993;Jiang et al, 1993;Jones and Gutkind, 1998;Dermott et al, 1999). Whereas Ga 12 proteins have been directly linked to regulatory molecules such as the Rho-directed guanine nucleotide exchange factor p115 Hart et al, 1998) and the GTPase-activating protein RasGAP1 , the signi®cance of these interactions in relation to the developmental and oncogenic roles of Ga 12 proteins has not been clearly de®ned.…”

mentioning

confidence: 99%

Identification of a prostate-specific G-protein coupled receptor in prostate cancer

Xia

Ma²,

Wang³

et al. 2001

Oncogene

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Oncogenic mutant of Gα12 stimulates cell proliferation through cycloxygenase-2 signaling pathway

Cited by 28 publications

References 26 publications

Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor

Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

Identification of a prostate-specific G-protein coupled receptor in prostate cancer

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Oncogenic mutant of Gα12 stimulates cell proliferation through cycloxygenase-2 signaling pathway

Cited by 28 publications

References 26 publications

Characterization of Ca2+Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/EndothelinAReceptor

Characterization of Ca2+Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/EndothelinAReceptor

Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of COX inhibitors?

Identification of a prostate-specific G-protein coupled receptor in prostate cancer

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Product

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Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor

Characterization of Ca²⁺Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/Endothelin_AReceptor