Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention

2005 ◽  
Vol 23 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Andrew J. Dannenberg ◽  
Scott M. Lippman ◽  
Jason R. Mann ◽  
Kotha Subbaramaiah ◽  
Raymond N. DuBois
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Research Evidence ◽  
Growth Factor Receptor ◽  
Cancer Chemoprevention ◽  
Cyclooxygenase 2 ◽  
Natural Substances ◽  
Epidermal Growth ◽  
Cox 2

Understanding the mechanisms underlying carcinogenesis provides insights that are necessary for the development of therapeutic strategies to prevent cancer. Chemoprevention, the use of drugs or natural substances to inhibit carcinogenesis, is a rapidly evolving aspect of cancer research. Evidence is presented that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are potential pharmacologic targets to prevent cancer. In this paper, we review key data implicating a causal relationship between COX-2, EGFR, and carcinogenesis and possible mechanisms of action. We discuss evidence of crosstalk between COX-2 and EGFR in order to strengthen the rationale for combination chemoprevention, and review plans for a clinical trial that will evaluate the concept of combination chemoprevention targeting COX-2 and EGFR.

Cyclooxygenase-2 (COX-2), Epidermal Growth Factor Receptor (EGFR), and Her-2/neu Expression in Ovarian Cancer

2002 ◽  
Vol 85 (2) ◽  
pp. 305-310 ◽  
Author(s):  
G. Ferrandina ◽  
F.O. Ranelletti ◽  
L. Lauriola ◽  
F. Fanfani ◽  
F. Legge ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Cyclooxygenase 2 ◽  
Her 2 ◽  
Epidermal Growth ◽  
Cox 2

Clinicopathologic Implications of the Epidermal Growth Factor Receptor, Cyclooxygenase 2 Expression, and Human Papillomavirus Status in Squamous Cell Carcinoma of the Uterine Cervix in the Elderly

2011 ◽  
Vol 21 (2) ◽  
pp. 337-348 ◽  
Author(s):  
Giovanna Giordano ◽  
Tiziana D'Adda ◽  
Barbara Dal Bello ◽  
Francesca Brigati ◽  
Alessandra Bersiga ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Human Papillomavirus ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
The Elderly ◽  
Cyclooxygenase 2 ◽  
Hpv Status ◽  
Epidermal Growth ◽  
Cox 2

Objectives:To find information on invasive squamous cervical carcinoma in the elderly, 110 invasive squamous cervical carcinomas obtained from 2 groups of patients (aged <60 and >60 years) were analyzed for human papillomavirus (HPV) status by polymerase chain reaction study, for immunohistochemical epidermal growth factor receptor (EGFR), cyclooxygenase 2 (Cox-2) expression, and clinicopathologic features.Methods:The HPV status and the expression of Cox-2 and EGFR in the younger and older women were compared and correlated with the grading, staging neoplasm, and lymph nodal status, using Fisher test and Spearman nonparametric correlation test. Overall survival curves were drawn using Kaplan-Meier estimates and were compared using log-rank tests in the whole series of 110 patients. Multinomial logistic regression was also used.Results and Conclusions:The number of neoplasms with higher staging was significantly greater than those in the younger women (P= 0.04). The mortality was higher in the older group than in the younger patients (P= 0.006).In the elderly, the presence of HPV DNA in 65% of cases, and in the absence of sexual activity, could be due to reactivation of latent HPV infection, which might be due to an impairment of host immunologic response.The overexpression of Cox-2 in a number of cases was significantly higher in the older group than in the younger group (P= 0.032, Fisher exact test), but this immunoreactivity is not related to the staging, grading, EGFR expression, or to the presence of HPV.The simultaneous expression of Cox-2 and EGFR had a poor prognostic significance, showing lower survival rates than cases without this immunoreactivity (P= 0.002), on univariate analysis.On multivariate analysis, Cox-2 and EGFR immunopositivity did not reveal any correlation between these markers and prognosis probably because the number of cases considered was not particularly high.

Cyclooxygenase-2 (COX-2) and Epidermal Growth Factor Receptor (EGFR) Expression in Human Pituitary Macroadenomas

2003 ◽  
Vol 26 (Supplement 2) ◽  
pp. S75-S80 ◽  
Author(s):  
Courtnay W. Bloomer ◽  
Lawrence Kenyon ◽  
Elizabeth Hammond ◽  
Terry Hyslop ◽  
David W. Andrews ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Cyclooxygenase 2 ◽  
Human Pituitary ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Cox 2 ◽  
Pituitary Macroadenomas

Epidermal growth factor receptor transactivation is required for proteinase-activated receptor-2-induced COX-2 expression in intestinal epithelial cells

2012 ◽  
Vol 303 (1) ◽  
pp. G111-G119 ◽  
Author(s):  
Christina L. Hirota ◽  
France Moreau ◽  
Vadim Iablokov ◽  
Michael Dicay ◽  
Bernard Renaux ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Epithelial Cells ◽  
Growth Factor Receptor ◽  
Intestinal Epithelial ◽  
Kinase Signaling ◽  
Epidermal Growth ◽  
Cox 2

Proteinase-activated receptor (PAR)2, a G protein-coupled receptor activated by serine proteinases, has been implicated in both intestinal inflammation and epithelial proliferation. Cyclooxygenase (COX)-2 is overexpressed in the gut during inflammation as well as in colon cancer. We hypothesized that PAR2 drives COX-2 expression in intestinal epithelial cells. Treatment of Caco-2 colon cancer cells with the PAR2-activating peptide 2-furoyl-LIGRLO-NH2 (2fLI), but not by its reverse-sequence PAR2-inactive peptide, for 3 h led to an increase in intracellular COX-2 protein expression accompanied by a COX-2-dependent increase in prostaglandin E2 production. 2fLI treatment for 30 min significantly increased metalloproteinase activity in the culture supernatant. Increased epidermal growth factor receptor (EGFR) phosphorylation was observed in cell lysates following 40 min of treatment with 2fLI. The broad-spectrum metalloproteinase inhibitor marimastat inhibited both COX-2 expression and EGFR phosphorylation. The EGFR tyrosine kinase inhibitor PD153035 also abolished 2fLI-induced COX-2 expression. Although PAR2 activation increased ERK MAPK phosphorylation, neither ERK pathway inhibitors nor a p38 MAPK inhibitor affected 2fLI-induced COX-2 expression. However, inhibition of either Src tyrosine kinase signaling by PP2, Rho kinase signaling by Y27632, or phosphatidylinositol 3 (PI3) kinase signaling by LY294002 prevented 2fLI-induced COX-2 expression. Trypsin increased COX-2 expression through PAR2 in Caco-2 cells and in an EGFR-dependent manner in the noncancerous intestinal epithelial cell-6 cell line. In conclusion, PAR2 activation drives COX-2 expression in Caco-2 cells via metalloproteinase-dependent EGFR transactivation and activation of Src, Rho, and PI3 kinase signaling. Our findings provide a mechanism whereby PAR2 can participate in the progression from chronic inflammation to cancer in the intestine.

scholarly journals Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2113 ◽  
Author(s):  
Hwana Han ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
Growth Factor Receptor ◽  
Ags Cells ◽  
Epidermal Growth ◽  
Cox 2

Reactive oxygen species (ROS) contribute to the oncogenic phenotype of cancer cells by acting as signaling molecules for inducing proliferation. ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs) pathway. The Ras-dependent pathway promotes the activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB), a transcriptional modulator of cyclooxygenase-2 (COX-2) that induces cell proliferation. Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables. This study aims to investigate whether lycopene inhibits proliferation and induces apoptosis in gastric cancer AGS cells by suppressing the EGFR/Ras/MAPK and NF-κB-COX-2 signaling axis. Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio). Lycopene reduced the level of intracellular and mitochondrial ROS and decreased the activation of the ROS-mediated EGFR/Ras/extracellular signal-regulated kinase (ERK) and p38 MAPK pathways, thus leading to attenuation of the DNA-binding activity of NF-κB p50/p50 and the level of COX-2 gene expression. These results show that lycopene-induced apoptosis and inhibition of proliferation occur via inhibition of ROS-activated EGFR/Ras/ERK and p38 MAPK pathways and NF-κB-mediated COX-2 gene expression in AGS cells. In conclusion, consumption of lycopene-enriched foods could decrease the incidence of gastric cancer.

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