Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells

Kelley, Daniel J.; Mestre, Juan R.; Subbaramaiah, Kotha; Sacks, Peter G.; Schantz, Stimson P.; Tanabe, Tadashi; Inoue, H.; Ramonetti, John T.; Dannenberg, Andrew J.

doi:10.1093/carcin/18.4.795

Cited by 131 publications

(61 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a nicotine-nitrosated derivative, is the major carcinogenic component in cigarette smoke. Since the polycyclic aromatic hydrocarbon of tobacco smoke was reported to cause an increase in cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E 2 in normal and transformed oral epithelial cells in 1997 (Kelley et al, 1997), an interest in the role of COX-2 and its metabolites in tobacco carcinogen-related carcinoma has been increased.…”

Section: Introductionmentioning

confidence: 99%

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

Huang

Hsin

et al. 2010

Oncogene

View full text Add to dashboard Cite

The role of thromboxane A 2 (TxA 2 ) in smokingassociated lung cancer is poorly understood. This study was conducted to study the role of TxA 2 in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA 2 synthase (TxAS) expression and thromboxane B 2 (TxB 2 ) generation in cultured lung cancer cells, the result of which was supported by the increased level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor furegrelate and TxA 2 receptor antagonist SQ29548 completely blocked NNK-mediated cell survival and growth via inducting apoptosis. TxA 2 receptor agonist U46619 reconstituted a near-full survival and growth response to NNK when TxAS was inhibited, affirming the role of TxA 2 receptor in NNK-mediated cell survival and growth. Suppression of cyclic adenosine monophosphate response element binding protein (CREB) activity by its small interference RNA blocked the effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) also had a positive role. Altogether, our results have revealed that NNK stimulates TxA 2 synthesis and activates its receptor in lung cancer cells. The increased TxA 2 may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells.

show abstract

Section: Introductionmentioning

confidence: 99%

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

Huang

Hsin

et al. 2010

Oncogene

View full text Add to dashboard Cite

show abstract

“…The COX-2 gene is an earlyresponse gene that is up-regulated by proinflammatory stimuli, growth factors, oncogenes, carcinogens, and tumor-promoting phorbol esters. 4,5 Previous studies have suggested that COX-2 plays a role in carcinogenesis. Several epidemiologic investigations have reported a lower than expected rate of colorectal adenomas and carcinomas in persons taking nonsteroidal antiinflammatory drugs (NSAIDs), inhibitors of cyclooxygenase activity.…”

mentioning

confidence: 99%

Cyclooxygenase‐2 expression in human pituitary tumors

Vidal

Kovács

Bell

et al. 2003

Cancer

View full text Add to dashboard Cite

BACKGROUNDCyclooxygenase‐2 (COX‐2) plays a role in progression of colon, breast, pancreas, and lung carcinomas. The authors investigated COX‐2 expression in pituitary tumors.METHODSExpression of COX‐2 was evaluated in 164 surgically removed human pituitary tumors. Correlation of COX‐2 with MIB‐1, a cell proliferation marker, as well as angiogenesis, patient age, gender, tumor type, size, invasiveness, and metastatic potential was investigated.RESULTSCyclooxygenase‐2 immunoreactivity was confined to the cytoplasm of tumor cells, whereas the nuclei were unlabeled. Few normal peritumoral adenohypophysial cells showed slight COX‐2 cytoplasmic immunoreactivity. The staining intensity and the percentage of immunopositive cells were higher in tumors. Most pituitary tumors (96%) were COX‐2–immunopositive. Expression was strong in 60 (44%), moderate in 39 (28%), and weak in 32 (24%). Male gonadotroph adenomas and null cell adenomas showed a high level of COX‐2 expression. Growth hormone‐producing adenomas, prolactin‐producing adenomas, thyrotropic hormone‐producing adenomas, female gonadotroph adenomas, silent adrenocorticotropic hormone‐producing adenomas, and silent subtype 3 adenomas had a low level of COX‐2 expression. Significant correlation was demonstrated with patient age, but not with tumor size, invasiveness, and MIB‐1 labeling indices. Expression was medium to high in 76% of macroadenomas and in only 45% of microadenomas. Strong correlations were noted with angiogenesis markers, such as microvessel density and surface density.CONCLUSIONSCorrelation with angiogenesis suggests that COX‐2 may be involved in the regulation of angiogenesis in pituitary tumors. Phamacologic inhibition of COX‐2 activity might suppress angiogenesis in pituitary tumors and may provide a novel approach for medical therapy. Cancer 2003;97:2814–21. © 2003 American Cancer Society.DOI 10.1002/cncr.11387

show abstract

“…COX-1 is expressed constitutively in most tissues and may be responsible for housekeeping functions (4). In contrast, COX-2 is not detectable in most normal tissues or resting immune cells, but its expression can be induced by endotoxin, cytokines, growth factors, and carcinogens (5)(6)(7).…”

mentioning

confidence: 99%

Redundancy in the Signaling Pathways and Promoter Elements Regulating Cyclooxygenase-2 Gene Expression in Endotoxin-treated Macrophage/Monocytic Cells

Mestre¹,

Mackrell²,

Rivadeneira³

et al. 2001

Journal of Biological Chemistry

137

View full text Add to dashboard Cite

Macrophage expression of cyclooxygenase-2 (COX-2), the inducible isoform of COX, is up-regulated by proinflammatory stimuli both in vivo and in vitro. Here we investigated the mechanisms regulating COX-2 gene expression in macrophage/monocytic cells. Lipopolysaccharide (LPS) is known to induce de novo COX-2 mRNA expression in these cells. Transient cotransfections with a COX-2 promoter-luciferase construct and different expression vectors showed that LPS up-regulates COX-2 transcription through both mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. Cotransfections with expression vectors for dominant negative mutants of MAPK and PKC isoforms did not suppress the effects of LPS on COX-2. Electrophoretic mobility shift assays and transient transfection experiments with deleted and mutated variants of a COX-2 promoter-luciferase construct showed that NFB, NF-IL6, and CRE promoter sites mediate gene transcription independently in response to LPS treatment. In these experiments, isolated NFB, NF-IL6, and CRE promoter sites were less effective than the intact promoter in mediating COX-2 transcription. Cotransfections with mutated COX-2 promoter-luciferase constructs and expression vectors showed that each one of these promoter elements can be activated by LPS through both MAPK and PKC pathways to induce gene expression. In summary, there is redundancy in the signaling pathways and promoter elements regulating COX-2 transcription in endotoxin-treated cells of macrophage/ monocytic lineage.

show abstract

Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells

Cited by 131 publications

References 21 publications

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

Cyclooxygenase‐2 expression in human pituitary tumors

Redundancy in the Signaling Pathways and Promoter Elements Regulating Cyclooxygenase-2 Gene Expression in Endotoxin-treated Macrophage/Monocytic Cells

Contact Info

Product

Resources

About