Transcriptional Regulation of Basal Cyclooxygenase-2 Expression in Murine Lung Tumor-Derived Cell Lines by CCAAT/Enhancer-Binding Protein and Activating Transcription Factor/cAMP Response Element-Binding Protein

Wardlaw, Sarah A.; Zhang, Na; Belinsky, Steven A.

doi:10.1124/mol.62.2.326

Cited by 37 publications

(20 citation statements)

References 25 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). Recently, another study investigating the molecular mechanism of COX-2 expression in murine lung tumor cell lines suggested the importance of the C/EBP but not the CRE site (14), which is consistent with our results. However, their study did not show the importance of NF-κB in the aberrant expression of COX-2.…”

Section: Discussionsupporting

confidence: 93%

“…Wild-type and a series of mutant COX-2 promoters cloned upstream of the luciferase gene in the pXP2 vector were a generous gift from Harvey R. Herschman (University of California, Los Angeles) (14). Cells (10 4 /ml) were plated on 24-well plates and on the following day, cells were transfected with the indicated plasmids using the GenePORTER transfection reagent (Gene Therapy Systems, Inc., San Diego, CA).…”

Section: Assessment Of Apoptosismentioning

confidence: 99%

See 1 more Smart Citation

PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

Ikezoe¹,

Yang²,

Saitoh³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract. Aberrant expression of COX-2 occurs in many types of malignancies including colon and lung cancers, and is implicated in development and progression of cancer. The molecular mechanisms associated with aberrant expression of COX-2 in lung cancer cells remain to be fully elucidated. In this study, we found that non-small cell lung cancer (NSCLC) NCI-H520 and NCI-H460 cells constitutively expressed COX-2 and produced prostaglandin E 2 (PGE 2 ) as measured by Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Reporter assays showed that transcriptional regulation of COX-2 was blunted when either the NF-IL6 (C/EBPß) or nuclear factor-κB (NF-κB) binding site in the COX-2 promoter was mutated, suggesting that C/EBPß and NF-κB transcription factors have an important role in aberrant expression of COX-2 in these lung cancer cells. In addition, the eight herbal mixture PC-SPES (Lot. 5431219) caused growth arrest and apoptosis of NCI-H520 and NCI-H460 cells in association with blockade of NF-κB and downregulation of C/EBPß, resulting in down-regulation of COX-2 and PGE 2 in these cells. On the other hand, PC-SPES upregulated the level of C/EBPß in these cells. Taken together, C/EBPß and NF-κB may be promising molecular targets for COX-2 inhibition in lung cancer cells. PC-SPES might be useful in the adjuvant setting for the treatment of individuals with resected NSCLC as well as other types of cancer in which COX-2 is activated. IntroductionCyclooxygenase (COX) is the rate-limiting enzyme for the production of prostaglandins and thromboxanes from free arachidonic acid (1,2). Two forms of COX have been described; a constitutively expressed enzyme, COX-1 and an inducible enzyme, COX-2. COX-1 is ubiquitously expressed. COX-2 is an inducible protein which is an essential component of the inflammatory response, as well as involved in the repair of injury (3). Physiological activity of this enzyme provides a benefit to the organism; however, the aberrant or excessive expression of COX-2 has been implicated in a wide variety of pathologic processes including arthritis, carcinoma, as well as septic shock. Abnormal levels of this enzyme have been observed in many types of cancer including those from colon and lung; and studies implicate its involvement in development and progression of cancer (4-6). However, the molecular mechanisms of aberrant expression of COX-2 in cancer cells remain to be fully elucidated.PC-SPES contains a partially extracted mixture of eight herbs: Dendrantherma morifolium, Tzvel; Ganoderma Lucidium, Karst; Glycyrrhiza glabra L; Isatis indigotica, Fort; Panax pseudo-ginseng, Wall; Rabdosia rubescens; Scutellaria baicalensis, Georgi and Serenoa repens (7). In previous studies, we and others have shown that PC-SPES mediated an antiproliferative effect on prostate cancer cells in vivo and in vitro (8,9). Recently, we showed that PC-SPES inhibited the proliferation of colon cancer cells and prevented polyp formation in a murine colon cancer model, the Apc min mouse (10). These...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Assessment Of Apoptosismentioning

confidence: 99%

PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

Ikezoe¹,

Yang²,

Saitoh³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…COX-2 and iNOS expression are also transcriptionally regulated by C/EBP and CREB as well as NF-B, and these transcription factors may be synergistically or independently involved in the expression of this gene expression (26,43,44). In this study, CRE and C/EBPs were consistently activated by Pin1, and these transcription factors are active to increase COX-2 expression in Pin1-overexpressed chondrocytes.…”

Section: Discussionmentioning

confidence: 59%

“…COX-2 expression is transcriptionally regulated by C/EBP, CREB, and NF-B, either synergistically or independently (25,26). We therefore transfected GFP-HTB-94 and Pin1-HTB-94 cells with either a wild-type COX-2 promoter-luciferase chimeric construct that contained the 574-bp 5Ј-flanking region of human COX-2 gene, a C/EBP mutant with an NF-IL-6 site (Ϫ132/Ϫ124) mutation, an NF-B mutant (Ϫ223/Ϫ214), or a CRE/AP-1 mutant (Ϫ59/Ϫ53) (27).…”

Section: Pin1-dependent Simultaneous Activation Of Nf-b Creb and Cmentioning

confidence: 99%

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

Jeong

Pokharel

Lim

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints and subsequent destruction of cartilage and bone. Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological roles in several diseases, including cancer and neurodegeneration. We found that both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary cultured human chondrocytes showed increased basal expression of proinflammatory proteins (COX-2, inducible NO synthase, TNF-α, and IL-1β). Site-directed mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was coordinately regulated by NF-κB, CREB, and C/EBP. Gel shift, reporter gene, and Western blot analyses confirmed that NF-κB, CREB, and C/EBP were consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and COX-2 expression in the ankle tissues. Moreover, juglone dose dependently decreased the basal COX-2 expression in primary cultured chondrocytes from RA patients. These results demonstrate that Pin1 induction during RA progress stimulates proinflammatory protein expression by activating NF-κB, CREB, and C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.

show abstract

“…However, ATRA did not induce COX-2 in phorbol 12-myristate 13-acetate-differentiated U937 cells [31] whereas it suppressed COX-2 transcription in human mammary epithelial cells [36] . In another study ATRA repressed COX-2 promoter activity and COX-2 mRNA expression in several murine lung tumor-derived cell lines, yet it increased promoter activity and COX-2 mRNA expression significantly in another lung tumor-derived cell line [37] . These data indicate that the effect of ATRA on COX-2 expression is likely to be cell-specific and this may explain why RAR and RXR do not play any role in COX-2 upregulation by ATRA in human MC [7] .…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Alique

Lucio-Cazaña

et al. 2006

Pharmacology

View full text Add to dashboard Cite

All-trans retinoic acid (ATRA) increases the expression of COX-1 and COX-2 and the production of PGE₂, a prostaglandin with anti-inflammatory effects in human mesangial cells (MC). COX-2 increased through a transcriptional mechanism independent of retinoic acid receptors (RAR) and retinoid X receptors (RXR) and dependent on extracellular regulated kinase-1/2 (ERK1/2), that became phosphorylated 5 min after ATRA addition. Here, in rat MC, ATRA also upregulated COX isoenzymes and PGE₂ production, but not in the same way as in human MC: (1) PGE₂ production increased only slightly; (2) RAR and RXR were involved in the transcriptional upregulation of COX-2 by ATRA since the RAR-pan-antagonist AGN193109 or the RXR-pan-antagonist HX531 abolished the induction of COX-2 mRNA whereas the RAR-pan-agonist TTNPB or the RXR-pan-agonist AGN194204 induced expression of COX-2, and (3) ERK1/2 phosphorylation, though important for COX-2 upregulation, took more than 1 h. Therefore the regulation of COX by ATRA exhibits striking differences between human and rat MC.

show abstract

Transcriptional Regulation of Basal Cyclooxygenase-2 Expression in Murine Lung Tumor-Derived Cell Lines by CCAAT/Enhancer-Binding Protein and Activating Transcription Factor/cAMP Response Element-Binding Protein

Cited by 37 publications

References 25 publications

PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

Upregulation of Cyclooxygenases by Retinoic Acid in Rat Mesangial Cells

Contact Info

Product

Resources

About