Regulation of Cyclooxygenase-2 by Interferon γ and Transforming Growth Factor α in Normal Human Epidermal Keratinocytes and Squamous Carcinoma Cells

Matsuura, Hironori; Sakaue, Masaki; Subbaramaiah, Kotha; Kamitani, Hideki; Eling, Thomas E.; Dannenberg, Andrew J.; Tanabe, Tadashi; Inoue, H.; Arata, Jirô; Jetten, Anton M.

doi:10.1074/jbc.274.41.29138

Cited by 176 publications

(155 citation statements)

References 76 publications

(113 reference statements)

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“…This could be due to the stabilization of COX-2 mRNA (Dean et al, 1999;Lasa et al, 2000;Matsuura et al, 1999;Ridley et al, 1998), or increased transcription of the COX-2 gene (Dean et al, 1999;Subbaramaiah et al, 2000a) as shown in other systems. The fact that the p38 MAPK speci®c inhibitor, SB202190, decreases COX-2 promoter activity suggests that p38 MAPK pathway also plays a role in the transcriptional induction of the COX-2 gene by UVB.…”

Section: Discussionmentioning

confidence: 99%

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

et al. 2001

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It has been shown that UVB irradiation induces expression of COX-2 and up-regulation of COX-2 plays a functional role in UVB tumor promotion. In this study, we examined the cis-elements in the human COX-2 promoter that may be responsible for the UVB induction of COX-2. Analyses with the COX-2 promoter region revealed that the cyclic AMP responsive element near the TATA box was essential for both basal and UVB induced COX-2 expression. This was further supported by studies using a dominant negative mutant of CREB, which strongly inhibited the activity of COX-2 promoter. Electrophoretic mobility shift assays indicated that CREB and ATF-1 were the major proteins binding to the COX-2 CRE. CREB and ATF-1 were phosphorylated upon UVB treatment, and SB202190, a p38 MAPK inhibitor, decreased the phosphorylation of CREB/ATF-1 and suppressed COX-2 promoter activity. In contrast, treatment with forskolin, an activator of adenylyl cyclase, led to phosphorylation of CREB and ATF-1 and activation of COX-2 promoter. Finally, enhanced binding of phospho-CREB/ATF-1 to the COX-2 CRE was observed after UVB induction. Thus, one signaling pathway for UVB induction of human COX-2 involves activation of p38, subsequent phosphorylation of CREB/ATF-1, and activation of the COX-2 CRE through enhanced binding of phosphorylated CREB/ ATF-1. Oncogene (2001) 20, 5164 ± 5172.

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Section: Discussionmentioning

confidence: 99%

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

et al. 2001

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“…We have reported that bombesin stimulated COX-2 expression in RIE-1 cells transfected with gastrin-releasing peptide receptor involves both ERK and p38 MAPK (17). Similarly, ERK and p38 MAPK pathways mediate the induction of COX-2 expression by transforming growth factor-␣ and interferon-␥ in human epidermal keratinocytes and squamous carcinoma cells (34). JNK and p38 MAPK pathways regulate interleukin-1␤-stimulated COX-2 expression in renal mesangial cells (35).…”

Section: Discussionmentioning

confidence: 99%

Gastrin Stimulates Cyclooxygenase-2 Expression in Intestinal Epithelial Cells through Multiple Signaling Pathways

Guo¹,

Cheng²,

Jin³

et al. 2002

Journal of Biological Chemistry

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Gastrin is a hormone produced by G-cells in the normal gastric antrum. However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or endocrine factor in the initiation and progression of colorectal carcinoma. The molecular mechanisms involved have not been elucidated. Hypergastrinemia induced by Helicobacter pylori infection is associated with increased cyclooxygenase-2 (COX-2) expression in gastric and colorectal tissues, suggesting the possibility that gastrin up-regulates COX-2 expression in these tissues; this has not been confirmed. We report here that gastrin significantly increases the expression of COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of prostaglandin E 2 from a rat intestinal epithelial cell line transfected with the CCK-B receptor. These actions were dependent upon the activation of multiple MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal growth factor receptor; and the increased expression and activities of transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun, activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2 expression. This effect may contribute to this hormone-dependent gastrointestinal carcinogenesis, especially in the colon.Cyclooxygenase-2 (COX-2) 1 is an inducible enzyme catalyzing the rate-limiting step in prostaglandin synthesis, converting arachidonic acid to prostaglandin H 2 (1). A large body of genetic and biochemical evidence supports the important role of COX-2 in tumorigenesis, particularly in colorectal cancer (1). COX-2 is overexpressed in cancer cells and is associated with enhanced invasiveness (1). However, the molecular mechanisms leading to up-regulation of COX-2 in intestinal cells are not completely understood.Gastrointestinal hormones regulate gastrointestinal homeostasis by affecting cell proliferation, differentiation, apoptosis, and gene expression. Aberrant control of these biological processes is thought to play an important role in establishment of intestinal neoplasia (2, 3).Gastrin is a gastrointestinal hormone that is produced by G-cells in the normal gastric antrum (4). We (5) and others (6) have shown that expression of cholecystokinin B/gastrin receptors is increased in most colon cancers. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy (3,4,7,8). Ciccotosto et al. (9) reported that 69% of colon cancers contain fully processed gastrin and that 100% have detectable amounts of progastrin, reflecting aberrant production of both gastrin and progastrin by colon cancer. Watson et al. (10,11) showed that immune neutralization of gastrin ...

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“…Collectively, in cancer microenvironment, cancer-specific or non-specific immune cells that are recruited into cancer sites induce inflammation, a cellular process involving the release of a wide variety of inflammatory mediators including IFN-c [6], subsequently ensuing induction of various cellular proteins such as B7-H1 in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Interferon regulatory factor‐1 is prerequisite to the constitutive expression and IFN‐γ‐induced upregulation of B7‐H1 (CD274)

et al. 2006

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Majority of cancer cells upregulate co-inhibitory molecule B7-H1 which confers resistance to anti-tumor immunity, allowing cancers to escape from host immune surveillance. We addressed the molecular mechanism underlying the regulation of cancer-associated B7-H1 expression in response to interferon-c (IFN-c). Using promoter constructs in luciferase assay, the region between 202 and 320 bp from the translational start site is responsible for B7-H1 expression. Electrophoretic mobility shift assay, site-directed mutagenesis and knockdown experiment using siRNA revealed that interferon regulatory factor-1 (IRF-1) is primarily responsible for the constitutive B7-H1 expression as well as for the IFN-c-mediated B7-H1 upregulation in a human lung cancer cell line A549. Additionally, AG490, a Janus activated kinase/signal transducer and activator of transcription inhibitor, greatly abolished the responsiveness of A549 cells to IFN-c by reducing the IRF-1 transcription. Our findings support a critical role of IRF-1 in the regulation of constitutive and IFN-c-induced expression of B7-H1 in cancer cells.

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Regulation of Cyclooxygenase-2 by Interferon γ and Transforming Growth Factor α in Normal Human Epidermal Keratinocytes and Squamous Carcinoma Cells

Abstract: Treatment of normal human epidermal keratinocytes (NHEK) with interferon-␥ (IFN-␥

Cited by 176 publications

References 76 publications

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

Gastrin Stimulates Cyclooxygenase-2 Expression in Intestinal Epithelial Cells through Multiple Signaling Pathways

Interferon regulatory factor‐1 is prerequisite to the constitutive expression and IFN‐γ‐induced upregulation of B7‐H1 (CD274)

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