Prostaglandin E2 drives cyclooxygenase 2 expression via cyclic AMP response element activation in human pancreatic cancer cells

Pino, Maria Simona; Nawrocki, Steffan T.; Cognetti, F.; Abruzzese, James L.; Xiong, Henry Q.; McConkey, David J.

doi:10.4161/cbt.4.11.2138

Cited by 38 publications

(25 citation statements)

References 26 publications

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“…Moreover, it is known that EGFR is overexpressed in pancreatic cancer and activates NF-nB, which in turn activates cyclooxygenase-2 (COX-2), leading to the production of prostaglandin E 2 (PGE 2 ), which is known to activate the EGFR pathway through a feedback mechanism (25). There are also other mechanisms involved in the pathway reported by Pino et al (26), showing that PGE 2 drives COX-2 expression through a mechanism involving activation of the PGE 2 receptor (26). Resistance to cytotoxic therapy has been partly associated with constitutive activation of NF-nB (27).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis-inducing effect of erlotinib is potentiated by 3,3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer

Ali¹,

Banerjee

Ahmad

et al. 2008

Molecular Cancer Therapeutics

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Section: Introductionmentioning

confidence: 99%

Apoptosis-inducing effect of erlotinib is potentiated by 3,3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer

Ali¹,

Banerjee

Ahmad

et al. 2008

Molecular Cancer Therapeutics

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“…In the present study, several hundreds of genes showed changed expression in the tumor tissues from the EP2-knockout mice compared with tumor tissues from the wild-type mice. A reason for this could be that EP2 signaling in host tissues is involved in several different pathways that are important events in tumor cells associated with tumor progression, including angiogenesis, the upregulation of COX-2, the loss of E-cadherin expression and anti-apoptosis in stem cells (16,22,(25)(26)(27)(28). Prom-1, also known as CD133, and CD44 are well-known markers of cancer stem cells, indicating reduced gene expression in the tumor tissues from the EP2-knockout mice in the present study.…”

Section: Discussionmentioning

confidence: 99%

Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors

et al. 2016

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Abstract. Prostaglandin E 2 (PGE 2 ) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE 2 receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE 2 -producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including stemness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE 2 signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth.

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“…COX-2 gene responds to a diverse range of stimuli from growth factors or cytokines to physical or chemical stress by increasing expression (Smith, 2000;Hinz and Brune, 2002;Turini and DuBois, 2002;Warner and Mitchell, 2004). Several signaling transduction pathways have been shown to regulate COX-2 gene expression, including the Mitogen-Activated Protein Kinases (Smith, 2000), Protein Kinase A (Choudhary et al, 2004;Pino et al, 2005) or Protein Kinase C (Xuan et al, 2005). Although PI3K has been reported to mediate UV-B induced COX-2 expression in keratinocytes, it is not known whether PI3K is essential for COX-2 gene induction by a variety of stimuli or in different cell types.…”

Section: Introductionmentioning

confidence: 99%

LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

Sun

Шевелева

et al. 2008

Toxicology and Applied Pharmacology

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Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT) induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K independent mechanisms in regulating CT induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca 2+ concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT induced COX-2 expression in cardiomyocytes.

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Prostaglandin E2 drives cyclooxygenase 2 expression via cyclic AMP response element activation in human pancreatic cancer cells

Cited by 38 publications

References 26 publications

Apoptosis-inducing effect of erlotinib is potentiated by 3,3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer

Apoptosis-inducing effect of erlotinib is potentiated by 3,3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer

Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors

LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

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