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Mark A Nelson - One of the best experts on this subject based on the ideXlab platform.
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abstract 2300 microrna 101 mir 101 posttranscriptionally regulates the expression of EP4 Receptor in colon cancers
Cancer Research, 2012Co-Authors: Benjamin C Onyeagucha, Anupama Chandramouli, Melania E Mercadopimentel, Nisreen Abu Shahin, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Mark A NelsonAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The predominant product of cyclooxygenase (COX-2) in the colon, prostaglandin (PG) E2 promotes carcinogenesis. Expression of the PGE2 Receptor EP4 is upregulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. A bioinformatics search revealed a conserved target site for miR-101 within the EP4 Receptor-3′ UTR. In both colorectal cancer cell lines and human specimens, we observed an inverse correlation between miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 Receptor-3′-UTR. In contrast, a mutant EP4 Receptor-3′-UTR was unaffected. Ectopic expression miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 Receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, pharmacologic inhibition of EP4 Receptor signaling or silencing of EP4 Receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 Receptor is negatively regulated by miR-101. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2300. doi:1538-7445.AM2012-2300
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MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 Receptor in colon cancers.
Cancer biology & therapy, 2012Co-Authors: Anupama Chandramouli, Benjamin C Onyeagucha, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Melania E. Mercado-pimentel, Lenka Stankova, Nisreen Abu Shahin, Mark A NelsonAbstract:Purpose: Expression of the PGE2 Receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 Receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 Receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. Results: We observed an inverse correlation between the levels of miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase report...
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the EP4 Receptor antagonist l 161 982 blocks prostaglandin e2 induced signal transduction and cell proliferation in hca 7 colon cancer cells
Experimental Cell Research, 2007Co-Authors: Durga P Cherukuri, Ronald L Heimark, Robert N Young, Xiao B O Chen, Anne Christine Goulet, Yongxin Han, John W Regan, Emmanuelle J Meuillet, Mark A NelsonAbstract:Accumulating evidence indicates that elevated levels of prostaglandin E2 (PGE2) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE2 exerts its effects through four G-protein-coupled PGE Receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE2 to stimulate cell proliferation of human colon cancer cells. However, the EP Receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 Receptor antagonist, completely blocks PGE2-induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 Receptors may provide a novel therapeutic approach to the treatment of colon cancer.
Anupama Chandramouli - One of the best experts on this subject based on the ideXlab platform.
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abstract 2300 microrna 101 mir 101 posttranscriptionally regulates the expression of EP4 Receptor in colon cancers
Cancer Research, 2012Co-Authors: Benjamin C Onyeagucha, Anupama Chandramouli, Melania E Mercadopimentel, Nisreen Abu Shahin, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Mark A NelsonAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The predominant product of cyclooxygenase (COX-2) in the colon, prostaglandin (PG) E2 promotes carcinogenesis. Expression of the PGE2 Receptor EP4 is upregulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. A bioinformatics search revealed a conserved target site for miR-101 within the EP4 Receptor-3′ UTR. In both colorectal cancer cell lines and human specimens, we observed an inverse correlation between miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 Receptor-3′-UTR. In contrast, a mutant EP4 Receptor-3′-UTR was unaffected. Ectopic expression miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 Receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, pharmacologic inhibition of EP4 Receptor signaling or silencing of EP4 Receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 Receptor is negatively regulated by miR-101. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2300. doi:1538-7445.AM2012-2300
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MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 Receptor in colon cancers.
Cancer biology & therapy, 2012Co-Authors: Anupama Chandramouli, Benjamin C Onyeagucha, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Melania E. Mercado-pimentel, Lenka Stankova, Nisreen Abu Shahin, Mark A NelsonAbstract:Purpose: Expression of the PGE2 Receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 Receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 Receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. Results: We observed an inverse correlation between the levels of miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase report...
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the induction of s100p expression by the prostaglandin e2 pge2 EP4 Receptor signaling pathway in colon cancer cells
Cancer Biology & Therapy, 2010Co-Authors: Anupama Chandramouli, Melania E Mercadopimentel, Anthony J Hutchinson, Adriana Gibadulinova, Erik R Olson, Sally E Dickinson, Renee Shanas, Jennifer M Davenport, Janae Owens, Achyut K BhattacharyyaAbstract:Background: Prostaglandin E2 (PGE2) levels are frequently elevated in colorectal carcinomas. PGE2 is perceived via four transmembrane G protein coupled Receptors (EP1-4), among which the EP4 Receptor is most relevant. PGE2/EP4-Receptor interaction activates CREB via the ERK/MEK pathway. However, the downstream target genes activated by this pathway remained to be investigated.Methodology/Prinicipal Findings: Here, we have identified S100P (an EF-hand calcium binding protein) as a novel downstream target. We show by realtime RT-PCR that S100P mRNA levels are elevated in 14/17 (82%) colon tumor tissues as compared to paired adjacent normal colonic tissues. S100P expression is stimulated in the presence of PGE2 in a time dependent manner at mRNA and protein levels in colon, breast and pancreatic cancer cells. Pharmacological and RNAi-mediated inhibition of the EP4 Receptor attenuates PGE2-dependent S100P mRNA induction. RNAi-mediated knockdown of CREB inhibits endogenous S100P expression. Furthermore, using ...
Atsushi Ichikawa - One of the best experts on this subject based on the ideXlab platform.
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prostanoid EP4 Receptor is involved in suppression of 3t3 l1 adipocyte differentiation
Biochemical and Biophysical Research Communications, 2004Co-Authors: Hiroaki Tsuboi, Yukihiko Sugimoto, Takayuki Kainoh, Atsushi IchikawaAbstract:Prostaglandins (PGs) have been shown to play various roles in adipogenesis. In this study, we investigated on which PGE Receptor subtypes are involved in the inhibition of 3T3-L1 preadipocyte differentiation. The triglyceride content of cells, used as an index of differentiation, was decreased when PGE(2), the FP-agonist fluprostenol or dibutyryl cAMP, was exogenously added to differentiation cocktails. 3T3-L1 preadipocyte cells express mRNAs for the prostanoid EP4, FP, and IP Receptors. PGE(2) and the EP4 agonist AE1-329 increased cAMP levels in preadipocytes in a dose-dependent manner. AE1-329 suppressed the expression induction of differentiation marker genes such as resistin and peroxisome proliferator-activated Receptor-gamma. The inhibitory effect of PGE(2) but not that of fluprostenol was reversed by the addition of the EP4 antagonist AE3-208. AE3-208 mimicked the differentiation-promoting effects of indomethacin. These results suggest that the EP4 Receptor mediates the suppressive action of PGE(2) in 3T3-L1 adipocyte differentiation.
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two gs coupled prostaglandin e Receptor subtypes ep2 and EP4 differ in desensitization and sensitivity to the metabolic inactivation of the agonist
Molecular Pharmacology, 1996Co-Authors: Nobuhiro Nishigaki, Manabu Negishi, Atsushi IchikawaAbstract:There are at least four subtypes of prostaglandin E (PGE) Receptors. The EP1 and EP3 Receptors are coupled to Ca2+ mobilization and the inhibition of adenylate cyclase, respectively, and the EP2 and EP4 Receptors are coupled to the same signal transduction pathway, stimulation of adenylate cyclase. To identify the functional differences between EP2 and EP4 Receptors, we examined agonist-induced desensitization of these two Receptors using Chinese hamster ovary cells, which stably express these Receptors. The EP4 Receptor underwent short term agonist-induced desensitization, but no such desensitization was observed for the EP2 Receptor. In contrast, the EP2 and EP4 Receptors displayed similar patterns of down-regulation in response to prolonged exposure to PGE2. On the other hand, PGE2 is rapidly metabolized to 15-keto-PGE2 and, subsequently, to 13,14-dihydro-15-keto-PGE2. Thus, we compared the sensitivities of the two Receptors to these two metabolites. The EP4 Receptor markedly lost the response at the first metabolism, whereas the EP2 Receptor gradually lost the response according to the degree of metabolism, having higher sensitivity to the first metabolite, 15-keto-PGE2, than the EP4 Receptor. Therefore, the physiological significance of EP2 and EP4 may lie in their different sensitivities to agonist-induced short term desensitization and their differential susceptibilities to the metabolic inactivation of the agonist.
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two gs coupled prostaglandin e Receptor subtypes ep2 and EP4 differ in desensitization and sensitivity to the metabolic inactivation of the agonist
Folia Pharmacologica Japonica, 1996Co-Authors: Nobuhiro Nishigaki, Manabu Negishi, Atsushi IchikawaAbstract:Prostaglandin (PG) E Receptors are devided into four subtypes. The EP1 and EP3 Receptors are coupled to Ca2+ mobilization and the inhibition of adenylate cyclase, respectively, and the EP2 and EP4 Receptors are coupled to the same signal transduction pathway, stimulation of adenylate cyclase. To identify the functional differences between EP2 and EP4 Receptors, we examined agonist-induced desensitization of these two Receptors using Chinese hamster ovary cells, which stably express these Receptors. The EP4 Receptor underwent short term agonist-induced desensitization, but no such desensitization was observed for the EP2 Receptor. In contrast, the EP2 and EP4 Receptors displayed similar patterns of down-regulation in response to prolonged exposure to PGE2. On the other hand, PGE2 is rapidly metabolized to 15-keto-PGE2 and subsequently to 13, 14-dihydro-15-keto-PGE2. Thus, we compared the sensitivities of the two Receptors to these two metabolites. The EP4 Receptor markedly lost the response at the first metabolism, while the EP2 Receptor gradually lost the response according to the degree of metabolism, having higher sensitivity to the first metabolite, 15-keto-PGE2, than the EP4 Receptor. Therefore, the physiological significance of EP2 and EP4 may lie in their different sensitivity to agonist-induced short term desensitization, and their differential susceptibility to the metabolic inactivation of the agonist.
Achyut K Bhattacharyya - One of the best experts on this subject based on the ideXlab platform.
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abstract 2300 microrna 101 mir 101 posttranscriptionally regulates the expression of EP4 Receptor in colon cancers
Cancer Research, 2012Co-Authors: Benjamin C Onyeagucha, Anupama Chandramouli, Melania E Mercadopimentel, Nisreen Abu Shahin, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Mark A NelsonAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The predominant product of cyclooxygenase (COX-2) in the colon, prostaglandin (PG) E2 promotes carcinogenesis. Expression of the PGE2 Receptor EP4 is upregulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. A bioinformatics search revealed a conserved target site for miR-101 within the EP4 Receptor-3′ UTR. In both colorectal cancer cell lines and human specimens, we observed an inverse correlation between miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 Receptor-3′-UTR. In contrast, a mutant EP4 Receptor-3′-UTR was unaffected. Ectopic expression miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 Receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, pharmacologic inhibition of EP4 Receptor signaling or silencing of EP4 Receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 Receptor is negatively regulated by miR-101. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2300. doi:1538-7445.AM2012-2300
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MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 Receptor in colon cancers.
Cancer biology & therapy, 2012Co-Authors: Anupama Chandramouli, Benjamin C Onyeagucha, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Melania E. Mercado-pimentel, Lenka Stankova, Nisreen Abu Shahin, Mark A NelsonAbstract:Purpose: Expression of the PGE2 Receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 Receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 Receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. Results: We observed an inverse correlation between the levels of miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase report...
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the induction of s100p expression by the prostaglandin e2 pge2 EP4 Receptor signaling pathway in colon cancer cells
Cancer Biology & Therapy, 2010Co-Authors: Anupama Chandramouli, Melania E Mercadopimentel, Anthony J Hutchinson, Adriana Gibadulinova, Erik R Olson, Sally E Dickinson, Renee Shanas, Jennifer M Davenport, Janae Owens, Achyut K BhattacharyyaAbstract:Background: Prostaglandin E2 (PGE2) levels are frequently elevated in colorectal carcinomas. PGE2 is perceived via four transmembrane G protein coupled Receptors (EP1-4), among which the EP4 Receptor is most relevant. PGE2/EP4-Receptor interaction activates CREB via the ERK/MEK pathway. However, the downstream target genes activated by this pathway remained to be investigated.Methodology/Prinicipal Findings: Here, we have identified S100P (an EF-hand calcium binding protein) as a novel downstream target. We show by realtime RT-PCR that S100P mRNA levels are elevated in 14/17 (82%) colon tumor tissues as compared to paired adjacent normal colonic tissues. S100P expression is stimulated in the presence of PGE2 in a time dependent manner at mRNA and protein levels in colon, breast and pancreatic cancer cells. Pharmacological and RNAi-mediated inhibition of the EP4 Receptor attenuates PGE2-dependent S100P mRNA induction. RNAi-mediated knockdown of CREB inhibits endogenous S100P expression. Furthermore, using ...
Ronald L Heimark - One of the best experts on this subject based on the ideXlab platform.
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abstract 2300 microrna 101 mir 101 posttranscriptionally regulates the expression of EP4 Receptor in colon cancers
Cancer Research, 2012Co-Authors: Benjamin C Onyeagucha, Anupama Chandramouli, Melania E Mercadopimentel, Nisreen Abu Shahin, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Mark A NelsonAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The predominant product of cyclooxygenase (COX-2) in the colon, prostaglandin (PG) E2 promotes carcinogenesis. Expression of the PGE2 Receptor EP4 is upregulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. A bioinformatics search revealed a conserved target site for miR-101 within the EP4 Receptor-3′ UTR. In both colorectal cancer cell lines and human specimens, we observed an inverse correlation between miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 Receptor-3′-UTR. In contrast, a mutant EP4 Receptor-3′-UTR was unaffected. Ectopic expression miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 Receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, pharmacologic inhibition of EP4 Receptor signaling or silencing of EP4 Receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 Receptor is negatively regulated by miR-101. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2300. doi:1538-7445.AM2012-2300
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MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 Receptor in colon cancers.
Cancer biology & therapy, 2012Co-Authors: Anupama Chandramouli, Benjamin C Onyeagucha, Bonnie Lafleur, Ronald L Heimark, Achyut K Bhattacharyya, Melania E. Mercado-pimentel, Lenka Stankova, Nisreen Abu Shahin, Mark A NelsonAbstract:Purpose: Expression of the PGE2 Receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 Receptor is not known. The present study was conducted to investigate the regulation of EP4 Receptor by miRNAs. Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 Receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 Receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. Results: We observed an inverse correlation between the levels of miR-101 and EP4 Receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase report...
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the EP4 Receptor antagonist l 161 982 blocks prostaglandin e2 induced signal transduction and cell proliferation in hca 7 colon cancer cells
Experimental Cell Research, 2007Co-Authors: Durga P Cherukuri, Ronald L Heimark, Robert N Young, Xiao B O Chen, Anne Christine Goulet, Yongxin Han, John W Regan, Emmanuelle J Meuillet, Mark A NelsonAbstract:Accumulating evidence indicates that elevated levels of prostaglandin E2 (PGE2) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE2 exerts its effects through four G-protein-coupled PGE Receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE2 to stimulate cell proliferation of human colon cancer cells. However, the EP Receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 Receptor antagonist, completely blocks PGE2-induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 Receptors may provide a novel therapeutic approach to the treatment of colon cancer.